51 results on '"Vegi Ganga Modi Naidu"'
Search Results
2. Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH
- Author
-
Dinesh Mani Tripathi, Sumati Rohilla, Impreet Kaur, Hamda Siddiqui, Preety Rawal, Pinky Juneja, Vikash Kumar, Anupama Kumari, Vegi Ganga Modi Naidu, Seeram Ramakrishna, Subham Banerjee, Rekha Puria, Shiv K. Sarin, and Savneet Kaur
- Subjects
inflammation ,liver sinusoidal endothelial cells ,immunonano-lipocarriers ,non-alcoholic steatohepatitis ,targeted delivery ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
- Published
- 2021
- Full Text
- View/download PDF
3. Ameliorative effect of Dillenia indica fruits against doxorubicin-induced cardiomyocyte toxicity
- Author
-
Jagadeesh Kumar, Kalyani Tene, Ranadeep Gogoi, Kalyan Kumar, Deepak Bharadwaj Pemmaraju, Vegi Ganga Modi Naidu, and P. A. Shantanu
- Subjects
chemistry.chemical_classification ,Reactive oxygen species ,Cardiotoxicity ,Antioxidant ,biology ,medicine.medical_treatment ,Pharmacology ,Dillenia ,biology.organism_classification ,medicine.disease_cause ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Lactate dehydrogenase ,Toxicity ,medicine ,Doxorubicin ,Oxidative stress ,medicine.drug - Abstract
Drug-induced cardiotoxicity is a significant concern in cancer patients, and therefore cardio-oncology is gaining more attention. Doxorubicin (Dox) is a potent anticancer drug used against various malignancies, with cardiotoxicity as a dose-limiting factor. Although the mechanism of Dox-mediated cardiotoxicity is not fully understood, it is thought to encompass oxidative stress during the therapy leading to cardiotoxicity in cancer patients. Several oxidative stress-induced diseases and drug-induced toxicities can be effectively ameliorated using bioactive plant constituents. Dillenia indica (DI) is one such plant belonging to the family Dilleniaceae and is used as an ethno-medicinal agent for the treatment of various oxidative stress-mediated diseases like diabetes and cancer. In this study, we have evaluated the protective effect of the hydroalcoholic extract of Dillenia indica fruits (HADI) against the Dox-induced cardiomyocyte toxicity. The HADI was further evaluated for its efficacy in a Dox-induced cardiotoxicity models. Antioxidant assays (ABTS and DPPH) revealed a strong antioxidant potential of HADI. In vitro assay results indicated that pre-treatment with HADI had shown protective activity and reduced the ROS generation in H9c2 cell line. Non-invasive methods like high-frequency ultrasonography and electrocardiography were applied to evaluate the real time cardiac parameters. It was also found that pre-treatment with HADI restored functional parameters like ejection fraction, stroke volume as well as elevation of the T wave induced by Dox. Whereas the Dox treated mice had elevated levels of cardiac functional enzymes like creatinine kinase (CK-MB) and lactate dehydrogenase indicating the severity of cardiomyocyte toxicity. The results indicated that HADI pre-treatment has significantly reduced the upregulated enzyme levels. Taken together, our findings indicated that HADI ameliorated the Dox-induced cardiomyocyte toxicity by modulating the upregulated reactive oxygen species.
- Published
- 2020
4. Characteristics of Molecularly Engineered Anticancer Drug Conjugated Organic Nanomicelles for Site-Selective Cancer Cell Rupture and Growth Inhibition of Tumor Spheroids
- Author
-
Shalini Dimri, Vegi Ganga Modi Naidu, Rohit Srivastava, Gayathri Ravichandran, Abhijit De, Rajendra Prasad, and Nishant Kumar Jain
- Subjects
chemistry.chemical_classification ,Biodistribution ,biology ,Biochemistry (medical) ,Biomedical Engineering ,Peptide ,General Chemistry ,Conjugated system ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Cancer stem cell ,Cancer cell ,Cancer research ,biology.protein ,medicine ,Antibody ,Growth inhibition ,Niclosamide ,medicine.drug - Abstract
Site-selective uptake and specific biodistribution of chemotherapeutic drugs are essential prerequisites for targeted cancer therapy. Especially, antibody and peptide conjugated drugs have been attempted as localized therapeutic agents. However, the characteristics of drug conjugated nanosystems are less explored, which are limited with their toxicity, low therapeutic efficacy, complicated synthesis, and high costs. Herein, we report a biocompatible (about 95%) molecularly engineered anticancer drug conjugated nanomicelles (∼200 nm in size) for site-selective CD44 overexpressed cancer cell rupture and tumor growth inhibition. Microscopic analysis demonstrates the distinct visualization of organic-organic interfaces (∼5 nm), which are corroborated with spectroscopic measurements confirmed the conjugation of niclosamide drug with hyaluronic acid (NIC-HA). Uniformly distributed hemocompatible (about 99%) organic nanomicelles exhibit the cellular membrane and cytoplasmic targeting with significant cellular rupture (IC
- Published
- 2020
5. Multifunctional Synthetic Amphiphile for Niche Therapeutic Applications: Mitigation of MRSA Biofilms and Potential in Wound Healing
- Author
-
Poulomi Dey, Aiyagari Ramesh, Vegi Ganga Modi Naidu, Gopal Das, and Eswara Rao Puppala
- Subjects
integumentary system ,Chemistry ,Biochemistry (medical) ,Biomedical Engineering ,Biofilm ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease_cause ,Microbiology ,Biomaterials ,Staphylococcus aureus ,Amphiphile ,medicine ,Wound healing - Abstract
The relentless menace of implant- and skin wound-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms demands the design of therapeutics that have an edge ove...
- Published
- 2022
6. Chemistry of herbal biomolecules
- Author
-
Deepak Bharadwaj Pemmaraju, Vegi Ganga Modi Naidu, Jagadeesh Kumar Gangasani, U.S.N. Murthy, and Aravind Kumar Rengan
- Subjects
chemistry.chemical_classification ,Chemistry ,Biomolecule ,Nanotechnology - Published
- 2022
7. Polymeric Core–Shell Combinatorial Nanomedicine for Synergistic Anticancer Therapy
- Author
-
Vegi Ganga Modi Naidu, Navneet Kaur, Nishant Kumar Jain, Asifkhan Shanavas, Rajendra Prasad, Maruthi Prasanna, Dhirendra Bahadur, Rohit Srivastava, and Dinesh Thummuri
- Subjects
Drug ,Biocompatibility ,General Chemical Engineering ,media_common.quotation_subject ,General Chemistry ,Article ,chemistry.chemical_compound ,Chemistry ,chemistry ,Docetaxel ,Cancer cell ,medicine ,Biophysics ,Nanomedicine ,Doxorubicin ,Growth inhibition ,QD1-999 ,medicine.drug ,Combination drug ,media_common - Abstract
Core–shell nanostructures are promising platforms for combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide-co-glycolide) (cmcPLGA) core–shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core–shell nanostructures are tested for combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment. The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles from fairly negative (−13 mV) to near neutral (−2 mV) while moving from a physiological pH (7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different cancer cells compared to free drug treatment. Importantly, Dox–Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower drug concentrations as compared to single-drug control groups. The observed promising performance of dual-drug formulation is due to the G2/M phase arrest and apoptosis.
- Published
- 2019
8. A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis
- Author
-
Elina Khatoon, Vegi Ganga Modi Naidu, Ajaikumar B. Kunnumakkara, Eswara Rao Puppala, Kishore Banik, Krishan Kumar Thakur, and Mangala Hegde
- Subjects
Curcumin ,Drug Compounding ,Biological Availability ,Inflammation ,Disease ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,In vivo ,Medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Gene ,Mice, Inbred BALB C ,business.industry ,Sequence Analysis, RNA ,Computational Biology ,Galactose ,General Medicine ,Drug Combinations ,Trigonella ,chemistry ,Chronic Disease ,Female ,medicine.symptom ,business - Abstract
Background Chronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies. Purpose/study design A novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases. Methods The whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server. Results The results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC Conclusion Overall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases.
- Published
- 2021
9. Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH
- Author
-
Seeram Ramakrishna, Savneet Kaur, Subham Banerjee, Impreet Kaur, Hamda Siddiqui, Vegi Ganga Modi Naidu, Rekha Puria, Dinesh M. Tripathi, Anupama Kumari, Pinky Juneja, Preety Rawal, Shiv Kumar Sarin, Vikash Kumar, and Sumati Rohilla
- Subjects
Male ,liver sinusoidal endothelial cells ,QH301-705.5 ,Inflammation ,immunonano-lipocarriers ,Article ,Catalysis ,Proinflammatory cytokine ,Inorganic Chemistry ,Mice ,Immune system ,Downregulation and upregulation ,Non-alcoholic Fatty Liver Disease ,hemic and lymphatic diseases ,medicine ,Animals ,Gene silencing ,RNA, Small Interfering ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Chemistry ,Cell adhesion molecule ,Organic Chemistry ,targeted delivery ,Endothelial Cells ,General Medicine ,medicine.disease ,Computer Science Applications ,Mice, Inbred C57BL ,Endothelial stem cell ,Disease Models, Animal ,RNAi Therapeutics ,Liver ,inflammation ,Core Binding Factor Alpha 2 Subunit ,embryonic structures ,Cancer research ,RNA Interference ,non-alcoholic steatohepatitis ,medicine.symptom ,Steatohepatitis - Abstract
Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
- Published
- 2021
- Full Text
- View/download PDF
10. Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach
- Author
-
G. Jagadeesh Kumar, Upadhyayula Suryanarayana Murty, Kalyani Tene, P. Eswara Rao, Vegi Ganga Modi Naidu, M. Kalyan Kumar, Ranadeep Gogoi, G. Basveshwar, Deepak Bharadwaj Pemmaraju, and Pramod Kumar
- Subjects
Pharmacology ,Cardiotoxicity ,ABTS ,DPPH ,ultrasonography ,RM1-950 ,Syringic acid ,doxorubicin ,chemistry.chemical_compound ,chemistry ,Polyphenol ,dillenia pentagyna roxb ,cardioprotection ,Toxicity ,medicine ,oxidative stress ,Pharmacology (medical) ,Doxorubicin ,Gallic acid ,Therapeutics. Pharmacology ,medicine.drug - Abstract
Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP’s bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.
- Published
- 2021
11. Silkworm Silk Scaffolds Functionalized with Recombinant Spider Silk Containing a Fibronectin Motif Promotes Healing of Full-Thickness Burn Wounds
- Author
-
Naresh Thatikonda, Tshewuzo-u Lohe, Vegi Ganga Modi Naidu, Dimple Chouhan, Biman B. Mandal, and My Hedhammar
- Subjects
Scaffold ,biology ,Chemistry ,fungi ,0206 medical engineering ,Biomedical Engineering ,Fibroin ,02 engineering and technology ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,law.invention ,Biomaterials ,Fibronectin ,Full thickness burn ,SILK ,law ,biology.protein ,Recombinant DNA ,Spider silk ,0210 nano-technology ,Wound healing ,Biomedical engineering - Abstract
Full-thickness cutaneous wounds, such as deep burns, are complex wounds that often require surgical interventions. Herein, we show the efficacy of acellular grafts that can be made available off-the-shelf at an affordable cost using silk biomaterials. Silkworm silk fibroin (SF), being a cost-effective and natural biopolymer, provides essential features required for the fabrication of three-dimensional constructs for wound-healing applications. We report the treatment of third-degree burn wounds using a freeze-dried microporous scaffold of Antheraea assama SF (AaSF) functionalized with a recombinant spider silk fusion protein FN-4RepCT (FN-4RC) that holds the fibronectin cell binding motif. In order to examine the healing efficiency of functionalized silk scaffolds, an in vivo burn rat model was used, and the scaffolds were implanted by a one-step grafting procedure. The aim of our work is to investigate the efficacy of the developed acellular silk grafts for treating full-thickness wounds as well as to examine the effect of recombinant spider silk coatings on the healing outcomes. Following 14-day treatment, AaSF scaffolds coated with FN-4RC demonstrated accelerated wound healing when compared to the uncoated counterpart, commercially used DuoDERM dressing patch, and untreated wounds. Histological assessments of wounds over time further confirmed that functionalized silk scaffolds promoted wound healing, showing vascularization and re-epithelialization in the initial phase. In addition, higher extent of tissue remodeling was affirmed by the gene expression study of collagen type I and type III, indicating advanced stage of healing by the silk treatments. Thus, the present study validates the potential of scaffolds of combined silkworm silk and FN-4RC for skin regeneration.
- Published
- 2019
12. Lipopolysaccharide exacerbates chronic restraint stress-induced neurobehavioral deficits: Mechanisms by redox imbalance, ASK1-related apoptosis, autophagic dysregulation
- Author
-
P. A. Shantanu, Vegi Ganga Modi Naidu, Vijaya Kumar Gangipangi, Basveshwar Gawali, Nitika Gupta, Sahabuddin Ahmed, Mohit Kwatra, and Samir Ranjan Panda
- Subjects
Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Inflammation ,Apoptosis ,Pathogenesis ,chemistry.chemical_compound ,Mice ,Neurochemical ,Internal medicine ,medicine ,Autophagy ,Animals ,ASK1 ,Biological Psychiatry ,Depressive Disorder, Major ,business.industry ,Psychiatry and Mental health ,Endocrinology ,Monoamine neurotransmitter ,chemistry ,medicine.symptom ,business ,Oxidation-Reduction - Abstract
Major depressive disorder (MDD) is the foremost leading psychiatric illness prevailing around the globe. It usually exists along with anxiety and other clinical conditions (cardiovascular, cancer, neurodegenerative diseases, and infectious diseases). Chronic restraint stress (RS) and LPS-induce neurobehavioral alterations in rodent models however their interaction studies in association with the pathogenesis of MDD are still unclear. Therefore, the current study was aimed to investigate the LPS influence on chronic RS mediated redox imbalance, apoptosis, and autophagic dysregulation in the hippocampus (HIP) and frontal cortex (FC) of mice brain. Male Balb/c mice were exposed to 28 days consecutive stress (6h/day) with a single-dose LPS challenge (0.83 mg/kg, i.p.) on the last day (Day 28). In addition, we also carried out separate study to understand physiological relevance, where we used the DSS (dextran sulfate sodium), a water soluble polysaccharide (negatively charged) and studied its influence on RS induced neurobehavioral and certain neurochemical anomalies. The obtained results in RS and RS + LPS animal groups showed significant immune dysfunction, depleted monoamines, lowered ATP & NAD level, elevated serum CORT level, serum and brain tissues IL-1β/TNF-α/IL-6, SOD activity but reduced CAT activity. Furthermore, the redox perturbation was found where significantly upregulated P-NFκB p65, Keap-1, Prx-SO3 and downregulated Nrf2, Srx1, Prx2 protein expression was seen in RS + LPS mice. The apoptosis signaling (P-ASK1, P-p38 MAPK, P-SAPK/JNK, cleaved PARP, cleaved Caspase-3, Cyto-C), autophagic impairment (p62, LC3II/I) were noticed in HIP and FC of RS and RS + LPS grouped animals. Our new findings provide a complex interplay of chemical (LPS) and physical (RS) stressors where both single dose LPS challenge and 3% DSS in drinking water (for 7 days) exaggerated chronic RS-induced inflammation, lowered redox status, increased apoptosis and dysregulated autophagy leading drastic neurobehavioral alterations in the mice.
- Published
- 2021
13. Biomaterials in treatment of Alzheimer's disease
- Author
-
Gautam Singhvi, Amit Alexander, Hafiz Ahmed, Vegi Ganga Modi Naidu, Sunil Kumar Dubey, Eluri Prathyusha, Prashant Kesharwani, and Mukta Agrawal
- Subjects
0301 basic medicine ,Drug ,Side effect ,media_common.quotation_subject ,Population ,Nanotechnology ,Biocompatible Materials ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Drug Delivery Systems ,Alzheimer Disease ,Animals ,Humans ,education ,media_common ,Liposome ,education.field_of_study ,Drug Carriers ,Chemistry ,Extracellular Polymeric Substance Matrix ,Brain ,Cell Biology ,Controlled release ,030104 developmental biology ,Colloidal gold ,Nanoparticles ,Nanocarriers ,Drug carrier ,030217 neurology & neurosurgery - Abstract
Alzheimer's disease (AD) is a non-recoverable progressive neurodegenerative disorder most prevalent but not limited to the old age population. After all the scientific efforts, there are still many unmet criteria and loopholes in available treatment and diagnostic strategies, limiting their efficacy. The poor drug efficacy is attributed to various biological hurdles, including blood-brain barrier (BBB) and peripheral side effects as most prominent ones and the lack of promising carriers to precisely deliver the drug to the brain by conserving its therapeutic potency. The increasing disease prevalence and unavailability of effective therapy calls for developing a more innovative, convenient and affordable way to treat AD. To fulfill such need, researchers explored various biomaterials to develop potential vectors or other forms to target the bioactives in the brain by preserving their inherent properties, improving the existing lacuna like poor solubility, permeability and bioavailability etc. and minimize the side effect. The unique characteristic properties of biomaterials are used to develop different drug carriers, surface modifying target active ligands, functional carriers, drug conjugate, biosensing probe, diagnostic tool and many more. The nanoparticulate system and other colloidal carriers like hydrogel and biodegradable scaffold can effectively target the drug moieties to the brain. Also, the use of different target-acting ligands and stimuli-responsive carriers assures the site-specificity and controlled release at the desired site by interaction with receptors and various exo- and endogenous stimuli. This review article has highlighted the application of biomaterials for targeting the drug to the brain and as promising diagnostic tools to detect the markers for better AD management. The work particularly focuses on the use of biomaterials as smart drug carriers including pH, thermo, photo, electro and magnetically triggered system; novel drug carriers for brain targeting including polymeric carriers (polymeric nanoparticle, dendrimer and polymeric micelle); lipid carrier (liposome, nanoemulsion, NLC and SLN); inorganic nanoparticles (quantum dots, gold nanoparticles etc.); and other drug vectors (hydrogel, biodegradable scaffold, and carbon nanotube) in treatment of AD. It also highlighted the application of some novel carrier systems and biomaterials as biosensor and other diagnostic tools for early and precise AD diagnosis.
- Published
- 2020
14. Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death
- Author
-
Vegi Ganga Modi Naidu, Samir Ranjan Panda, Basveshwar Gawali, Sahabuddin Ahmed, and Mohit Kwatra
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Apoptosis ,Tropomyosin receptor kinase B ,CREB ,7,8-Dihydroxyflavone ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Animals ,Humans ,Cyclic AMP Response Element-Binding Protein ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Pharmacology ,Membrane Potential, Mitochondrial ,Neurons ,Membrane Glycoproteins ,biology ,Cell Death ,Chemistry ,Brain-Derived Neurotrophic Factor ,Biochemistry (medical) ,Cell Biology ,Protein-Tyrosine Kinases ,Flavones ,Nitro Compounds ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,Huntington Disease ,Neuroprotective Agents ,nervous system ,Mitochondrial biogenesis ,030220 oncology & carcinogenesis ,biology.protein ,Phosphorylation ,Phosphatidylinositol 3-Kinase ,Propionates ,Proto-Oncogene Proteins c-akt ,Neurotrophin ,Signal Transduction - Abstract
Striatal neurons depends on an afferent supply of brain-derived neurotrophic factor-(BDNF) that explicitly interacts with tropomyosin receptor kinase B (TrkB) receptor and performs sundry functions including synaptic plasticity, neuronal differentiation and growth. Therefore, we aimed to scrutinize an active molecule that functions identical to BDNF in activating TrkB receptor and it’s downstream targets for restoring neuronal survival in Huntington disease (HD). Data from in vitro Neuro-2a cell line showed that treatment with 7,8-dihydroxyflavone (7,8-DHF), improved 3-nitropropionic acid (3-NP) induced neuronal death by stabilizing the loss of mitochondrial membrane potential and transiently increased the activity of cAMP-response element-binding protein (CREB) and BDNF via TrkB receptor activation. Consistent with in vitro findings, our in vivo results stated that treatment with 7,8-DHF at a dose of 10 mg/kg body weight ameliorated various behavior alterations caused by 3-NP intoxication. Further histopathological and electron microscopy evidences from striatal region of 3-NP mice brain treated with 7,8-DHF showed more improved neurons with intact mitochondria and less autophagic vacuoles. Protein expression analysis of both in vitro and in vivo study showed that 7,8-DHF promotes neuronal survival through upregulation and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt at serine-473/threonine-308). Akt phosphorylation additionally phosphorylates Bad at serine-136 and inhibits its translocation to mitochondria thereby promoting mitochondrial biogenesis, enhanced ATP production and inhibit apoptosis mediated neuronal death. These aforementioned findings help in strengthening our hypothesis and has come up with a novel neuroprotective mechanism of 7,8-DHF against 3-NP induced neuronal death.
- Published
- 2020
15. Geometry encoded functional programming of tumor homing peptides for targeted drug delivery
- Author
-
Ruchika Goyal, Vegi Ganga Modi Naidu, T.R. Santhoshkumar, Gaurav Jerath, Vibin Ramakrishnan, Eswara Rao Puppala, Srikanth Ponneganti, R. Akhil, Aneesh Chandrasekharan, and Anupam Sarma
- Subjects
Fluorescence-lifetime imaging microscopy ,Pharmaceutical Science ,Peptide ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,02 engineering and technology ,law.invention ,03 medical and health sciences ,Drug Delivery Systems ,In vivo ,Confocal microscopy ,law ,Cell Line, Tumor ,Humans ,Peptide library ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Chemistry ,021001 nanoscience & nanotechnology ,Cell biology ,Targeted drug delivery ,Pharmaceutical Preparations ,Drug delivery ,Female ,0210 nano-technology ,Peptides ,Homing (hematopoietic) - Abstract
Poly-peptide molecules have shown promising applications in drug delivery and tumor targeting. A series of tumor homing peptides were designed by exhaustively sampling low energy geometrical basins of amino acids at specific sites of a peptide molecule to induce a conformational lock. This peptide library was pruned to a limited set of eight molecules, employing electrostatic interactions, docking, and molecular dynamics simulations. These designed and optimized peptides were synthesized and tested on various cell lines, including breast cancer (MDA-MB-231), cervical cancer (HeLa), osteosarcoma (U2-OS), and non-cancerous mammary epithelial cells (MCF-10A) using confocal microscopy and flow cytometry. Peptides show differential uptake in cancerous MDA-MB-231, HeLa, U2-OS, and non-cancerous MCF-10A cells. Confocal imaging verified their ability to penetrate even in 3D tumorospheres of MDA-MB-231 cells. Further, experiments of mitochondrial membrane potential depolarization and Caspase-3 activation confirmed that their cytotoxic effects are by apoptosis. Homing ability of the designed peptides in in vivo system and fluorescence imaging with clinical samples of human origin have further confirmed that the in vitro studies are qualitatively identical and quantitatively comparable in their ability to selectively recognize tumor cells. Overall, we present a roadmap for the functional programming of peptide-based homing and penetrating molecules that can perform selective tumor targeting.
- Published
- 2020
16. Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease
- Author
-
Upadhyayula Suryanarayana Murty, Vegi Ganga Modi Naidu, Samir Ranjan Panda, Sahabuddin Ahmed, and Mohit Kwatra
- Subjects
0301 basic medicine ,Inflammasomes ,Andrographolide ,Ubiquitin-Protein Ligases ,Immunology ,Neuroprotection ,Parkin ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Mitophagy ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Endocrine and Autonomic Systems ,Chemistry ,Neurodegeneration ,Autophagy ,Inflammasome ,Parkinson Disease ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Microglia ,Diterpenes ,NLRP3 inflammasome complex ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Cellular communication linking microglia activation and dopaminergic neuronal loss play an imperative role in the progression of Parkinson’s disease (PD); however, underlying molecular mechanisms are not precise and require further elucidation. NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation is extensively studied in context to microglial activation and progressive dopaminergic neuronal loss in PD. Several pathophysiological factors such as oxidative stress, mitochondrial dysfunction impaired mitophagy plays a crucial role in activating NLRP3 inflammasome complex. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia mediated neurodegeneration. In this study we have developed a model of inflammasome activation by combining LPS with a mitochondrial complex-I inhibitor MPP+. The idea of using MPP+ after priming mouse microglia with LPS was to disrupt mitochondria and release reactive oxygen species, which act as Signal 2 in augmenting NLRP3 assembly, thereby releasing potent inflammatory mediators such as active interleukin-1 beta (IL-1β) and IL-18. LPS-MPP+ combination was seen to impaired the mitophagy by inhibiting the initial step of autophagosome formation as evidenced by protein expression and confocal imaging data. Treatment with Andrographolide promoted the parkin-dependent autophagic flux formation in microglia; resulting in the removal of defective mitochondria which in turn inhibit NLRP3 inflammasome activation. Additionally, the neuroprotective role of Andrographolide in inhibiting NLRP3 activation together with salvage ATP level via promoting parkin-dependent mitophagy was seen in the substantial nigra par compacta (SNpc) region of mice brain. Furthermore, Andrographolide rescued the dopaminergic neuron loss and improved the behavioural parameters in animal model. Collectively, our results reveal the role of mitophagy in the regulation of NLRP3 inflammasome by removing defective mitochondria. In addition, andrographolide was seen to abate NLRP3 inflammasome activation in microglia and rescue dopaminergic neuron loss.
- Published
- 2020
17. Stimuli-responsive In situ gelling system for nose-to-brain drug delivery
- Author
-
Mukta Agrawal, Ajazuddin, Umesh Gupta, Vegi Ganga Modi Naidu, Upadhyayula Suryanarayana Murty, Swarnlata Saraf, Amit Alexander, V. Ravichandiran, Shailendra Saraf, Pramod Kumar, Anu Puri, Prashant Kesharwani, and Sunil Kumar Dubey
- Subjects
Drug ,0303 health sciences ,Mucociliary clearance ,Chemistry ,media_common.quotation_subject ,Pharmaceutical Science ,Brain ,02 engineering and technology ,Absorption (skin) ,Pharmacology ,021001 nanoscience & nanotechnology ,Smart polymer ,Dosage form ,03 medical and health sciences ,Nasal Absorption ,Nasal Mucosa ,Drug Delivery Systems ,Drug delivery ,Nasal administration ,0210 nano-technology ,Gels ,Administration, Intranasal ,030304 developmental biology ,media_common - Abstract
The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.
- Published
- 2020
18. Synthesis and Biological Evaluation of Thieno[2, 3-d ]pyrimidine-amides as Potential Anticancer Agents
- Author
-
Ahmed Kamal, Sowjanya Thatikonda, Vegi Ganga Modi Naidu, Srinivas Angapelly, Bathini Nagendra Babu, and Posa Venkata Sri Ramya
- Subjects
Pyrimidine ,010405 organic chemistry ,General Chemistry ,Cell cycle ,01 natural sciences ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Biochemistry ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Biological evaluation - Published
- 2018
19. Hepatoprotective Cocrystals and Salts of Riluzole: Prediction, Synthesis, Solid State Characterization, and Evaluation
- Author
-
Rahul B. Chavan, Nalini R. Shastri, Vegi Ganga Modi Naidu, Sridhar Balasubramanian, Rajesh Thipparaboina, and Balvant Yadav
- Subjects
Fumaric acid ,Synthon ,02 engineering and technology ,General Chemistry ,Syringic acid ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Combinatorial chemistry ,Cinnamic acid ,0104 chemical sciences ,Riluzole ,Ferulic acid ,chemistry.chemical_compound ,chemistry ,medicine ,Vanillic acid ,General Materials Science ,Solubility ,0210 nano-technology ,medicine.drug - Abstract
Riluzole is a drug, used to slow the course of amyotrophic lateral sclerosis. Due to its unique structure and functionalities, it is able to form both salts and cocrystals. This is a BCS class II drug with poor solubility and causes hepatotoxicity which limits its application. The present study aims toward development of novel solid forms of riluzole to address the said limitations. Apart from this, an attempt has been made to develop a prediction model using software tools to identify the appropriate synthons for formation of cocrystals. It was observed that out of 33 coformers selected, prediction results were in agreement with the experimental outcome for 25 coformers, which demonstrated the potential of the model developed. Seven new solid forms of riluzole, five cocrystals with ferulic acid, syringic acid, vanillic acid, cinnamic acid, and proline, and two salts with 2,4 dihydroxybenzoic acid and fumaric acid were successfully developed. All the solid forms were characterized by DSC, powder XRD, FTIR...
- Published
- 2018
20. Quercetin and piperine enriched nanostructured lipid carriers (NLCs) to improve apoptosis in oral squamous cellular carcinoma (FaDu cells) with improved biodistribution profile
- Author
-
Vishal Sharad Chaudhari, Upadhyayula Suryanarayana Murty, Basveshwar Gawali, Subham Banerjee, Pritam Saha, and Vegi Ganga Modi Naidu
- Subjects
Biodistribution ,Polyunsaturated Alkamides ,Apoptosis ,Pharmacology ,chemistry.chemical_compound ,Alkaloids ,Piperidines ,Oral administration ,Animals ,Humans ,Distribution (pharmacology) ,Tissue Distribution ,Benzodioxoles ,Particle Size ,Cytotoxicity ,IC50 ,Membrane Potential, Mitochondrial ,Squamous Cell Carcinoma of Head and Neck ,Fatty Acids ,In vitro ,Nanostructures ,Rats ,Drug Liberation ,chemistry ,Piperine ,Cancer cell ,Mouth Neoplasms ,Quercetin ,Drug Screening Assays, Antitumor ,Nanoparticle Drug Delivery System - Abstract
Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of 85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC50 concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer.
- Published
- 2021
21. Lithocholic acid-tryptophan conjugate (UniPR126) based mixed micelle as a nano carrier for specific delivery of niclosamide to prostate cancer via EphA2 receptor
- Author
-
Eswara Rao Puppala, N P Syamprasad, Vegi Ganga Modi Naidu, Amit Alexander, Arun Kumar Jannu, Basveshwar Gawali, Naveen Chella, Jagadeesh Kumar Gangasani, and Srujan Marepally
- Subjects
Male ,Lithocholic acid ,Bile acid ,medicine.drug_class ,Receptor, EphA2 ,Tryptophan ,Prostatic Neoplasms ,Pharmaceutical Science ,Pharmacology ,chemistry.chemical_compound ,chemistry ,In vivo ,Cell Line, Tumor ,Cancer cell ,medicine ,Humans ,Niclosamide ,Lithocholic Acid ,Receptor ,Wnt Signaling Pathway ,Micelles ,medicine.drug ,Conjugate - Abstract
Targeted delivery of chemotherapeutic agents is considered a prominent strategy for the treatment of cancer due to its site-specific delivery, augmented penetration, bioavailability, and improved therapeutic efficiency. In the present study, we employed UniPR126 as a carrier in a mixed nanomicellar delivery system to target and deliver anticancer drug NIC specifically to cancer cells via EphA2 receptors as these receptors are overexpressed in cancer cells but not in normal cells. The specificity of the carrier was confirmed from the significant enhancement in the uptake of coumarin-6 loaded mixed nanomicelle by EphA2 highly expressed PC-3 cells compared to EphA2 low expressed H4 cells. Further, niclosamide-loaded lithocholic acid tryptophan conjugate-based mixed nanomicelle has shown significant synergistic cytotoxicity in PC-3 but not in H4 cells. In vivo anticancer efficacy data in PC-3 xenograft revealed a significant reduction in the tumor volume (66.87%) with niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle, where pure niclosamide showed just half of the activity. Molecular signaling data by western blotting also indicated that niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle interfered with the EphA2 receptor signaling and inhibition of the Wnt/beta-catenin pathway and resulted in the synergistic anticancer activity compared to niclosamide pure drug.
- Published
- 2021
22. Synthesis of 2,5-Disubstituted-1,3,4-oxadiazole Derivatives and Their Evaluation as Anticancer and Antimycobacterial Agents
- Author
-
Bhaskar Kummari, Umarani Brahma, Sridhar Balasubramanian, Parsharamulu Rayam, Naveen Polkam, Jaya Shree Anireddy, and Vegi Ganga Modi Naidu
- Subjects
Veratric acid ,Antimycobacterial Agents ,010405 organic chemistry ,Stereochemistry ,medicine.drug_class ,Oxadiazole ,General Chemistry ,010402 general chemistry ,Antimycobacterial ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Bromide ,medicine ,1 3 4 oxadiazole derivatives ,Bioisostere - Abstract
A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by swapping the carboxylic motif to its oxadiazole bioisostere and have been screened for in vitro anticancer studies by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. All of them were well characterized by spectroscopic techniques. Among the screened compounds, 9 i (2-(2,5-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) demonstrated superior activity against MDA231 cells. Products 9 i displayed excellent activity against DU145, HCT15 and 10 i (2-(3,4-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) against MDA231 cells. Structure of 10 c (2-(3,4-dimethoxyphenyl)-5-(2,4,6-trimethoxyphenyl)-1,3,4-oxadiazole) was further authenticated through single crystal X-ray diffraction. Analogue 9 i have come out to be the best anticancer and antimycobacterial agent.
- Published
- 2017
23. Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy
- Author
-
Rohit Srivastava, Nishant Kumar Jain, Rajdip Bandyopadhyaya, Rajendra Prasad, Vegi Ganga Modi Naidu, M. C. Bavya, and R S Prabhuraj
- Subjects
Drug ,chemistry.chemical_classification ,Reactive oxygen species ,General Chemical Engineering ,media_common.quotation_subject ,Cell ,02 engineering and technology ,General Chemistry ,Pharmacology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Hyaluronic acid ,Cancer cell ,Zeta potential ,medicine ,Nanocarriers ,0210 nano-technology ,Niclosamide ,media_common ,medicine.drug - Abstract
Localized cancer rates are on an upsurge, severely affecting mankind across the globe. Timely diagnosis and adopting appropriate treatment strategies could improve the quality of life significantly reducing the mortality and morbidity rates. Recently, nanotherapeutics has precipitously shown increased efficacy for controlling abnormal tissue growth in certain sites in the body, among which ligand functionalized nanoparticles (NP) have caught much attention for improved survival statistics via active targeting. Our focus was to repurpose the antihelminthic drug, niclosamide (NIC), which could aid in inhibiting the abnormal growth of cells restricted to a specific region. The work here presents a one-pot synthesis of niclosamide encapsulated, hyaluronic acid functionalized core–shell nanocarriers [(NIC-PLGA NP)HA] for active targeting of localized cancer. The synthesized nanocarriers were found to possess spherical morphology with mean size of 150.8 ± 9 nm and zeta potential of −24.9 ± 7.21 mV. The encapsulation efficiency was found to be 79.19 ± 0.16% with a loading efficiency of 7.19 ± 0.01%. The nanohybrids exhibited extreme cytocompatibility upon testing with MDA-MB-231 and L929 cell lines. The rate of cancer cell elimination was approximately 85% with targeted cell imaging results being highly convincing. [(NIC-PLGA NP)HA] demonstrates increased cellular uptake leading to a hike in reactive oxygen species (ROS) generation, combating tumour cells aiding in the localized treatment of cancer and associated therapy.
- Published
- 2019
24. Emu oil based nano-emulgel for topical delivery of curcumin
- Author
-
Shweta Shrivastava, Sri Vishnu Kiran Rompicharla, Manish Kumar Jeengar, Ramakrishna Sistla, Vegi Ganga Modi Naidu, Naveen Chella, and Nalini R. Shastri
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Curcumin ,Administration, Topical ,Chemistry, Pharmaceutical ,Anti-Inflammatory Agents ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Carrageenan ,Excipients ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Pulmonary surfactant ,immune system diseases ,In vivo ,hemic and lymphatic diseases ,medicine ,Animals ,Edema ,Topical route ,Inflammation ,business.industry ,021001 nanoscience & nanotechnology ,Arthritis, Experimental ,Rats ,Surgery ,Disease Models, Animal ,030104 developmental biology ,Solubility ,chemistry ,Emu oil ,Drug delivery ,Nanoparticles ,Emulsions ,Swelling ,medicine.symptom ,0210 nano-technology ,business ,Oils - Abstract
Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.
- Published
- 2016
25. Corrigendum to 'Preparation, characterization, and cytotoxicity studies of niclosamide loaded mesoporous drug delivery systems' [Int. J. Pharm. 528 (2017) 202-214]
- Author
-
Vegi Ganga Modi Naidu, Rajesh Thipparaboina, Sowjanya Thatikonda, Vishwas Pardhi, Rahul B. Chavan, and Nalini R. Shastri
- Subjects
Chemistry ,INT ,Drug delivery ,medicine ,Pharmaceutical Science ,Cytotoxicity ,Mesoporous material ,Combinatorial chemistry ,Niclosamide ,medicine.drug - Published
- 2018
26. Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies
- Author
-
V. Lakshma Nayak, T. Srinivasa Reddy, Nagula Shankaraiah, Manish Kumar Jeengar, Kishna Ram Senwar, Pankaj Sharma, Ahmed Kamal, and Vegi Ganga Modi Naidu
- Subjects
Indoles ,Morpholines ,Antineoplastic Agents ,Apoptosis ,HeLa ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Spiro Compounds ,Fragmentation (cell biology) ,Cell Proliferation ,Pharmacology ,A549 cell ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Cytotoxins ,Cell growth ,Chemistry ,Cell Cycle ,Organic Chemistry ,Acridine orange ,General Medicine ,Triazoles ,Cell cycle ,biology.organism_classification ,Biochemistry ,Cell culture ,Drug Design ,Drug Screening Assays, Antitumor - Abstract
A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells.
- Published
- 2015
27. Anticancer effect of celastrol on human triple negative breast cancer: Possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways
- Author
-
V. Sudhakar Reddy, Shweta Shrivastava, Vegi Ganga Modi Naidu, G. Bhanuprakash Reddy, and Manish Kumar Jeengar
- Subjects
Cell Survival ,Clinical Biochemistry ,Apoptosis ,Breast Neoplasms ,Pathology and Forensic Medicine ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Annexin ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Chemistry ,Akt/PKB signaling pathway ,Triterpenes ,Mitochondria ,Cell biology ,Oxidative Stress ,Celastrol ,MCF-7 Cells ,Cancer research ,Phosphorylation ,Signal transduction ,Pentacyclic Triterpenes ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Signaling via the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is crucial for divergent physiological processes including transcription, translation, cell-cycle progression and apoptosis. The aim of work was to elucidate the anti-cancer effect of celastrol and the signal transduction pathways involved. Cytotoxic effect of celastrol was assessed by MTT assay on human triple negative breast cancer cells (TNBCs) and compared with that of MCF-7. Apoptosis induction was determined by AO/EtBr staining, mitochondrial membrane potential by JC-1, Annexin binding assays and modulation of apoptotic proteins and its effect on PI3K/Akt/mTOR pathway by western blotting. Celastrol induced apoptosis in TNBC cells, were supported by DNA fragmentation, caspase-3 activation and PARP cleavage. Meanwhile, celastrol triggered reactive oxygen species production with collapse of mitochondrial membrane potential, down-regulation of Bcl-2 and up-regulation of Bax expression. Celastrol effectively decreased PI3K 110α/85α enzyme activity, phosphorylation of Aktser473 and p70S6K1 and 4E-BP1. Although insulin treatment increased the phosphorylation of Aktser473, p70S6K1, 4E-BP1, celastrol abolished the insulin mediated phosphorylation. It clearly indicates that celastrol acts through PI3k/Akt/mTOR axis. We also found that celastrol inhibited the Akt/GSK3β and Akt/NFkB survival pathway. PI3K/Akt/mTOR inhibitor, PF-04691502 and mTOR inhibitor rapamycin enhanced the apoptosis-inducing effect of celastrol. These data demonstrated that celastrol induces apoptosis in TNBC cells and indicated that apoptosis might be mediated through mitochondrial dysfunction and PI3K/Akt signaling pathway.
- Published
- 2015
28. Abietic acid attenuates RANKL induced osteoclastogenesis and inflammation associated osteolysis by inhibiting the NF-KB and MAPK signaling
- Author
-
Vegi Ganga Modi Naidu, Veerabhadra Swamy Challa, Lalita Guntuku, Ravinder Naik Ramavat, and Dinesh Thummuri
- Subjects
0301 basic medicine ,Osteolysis ,Physiology ,Clinical Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,In vivo ,Osteoclast ,Osteogenesis ,medicine ,Animals ,Humans ,Polylysine ,Phosphorylation ,Receptor ,Inflammation ,Mitogen-Activated Protein Kinase Kinases ,Osteoblasts ,biology ,NFATC Transcription Factors ,Activator (genetics) ,Phosphatidylethanolamines ,RANK Ligand ,NF-kappa B ,NF-κB ,Cell Differentiation ,Cell Biology ,medicine.disease ,Actins ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,RANKL ,030220 oncology & carcinogenesis ,Abietanes ,Cancer research ,biology.protein ,Osteoporosis ,Signal Transduction - Abstract
Osteoporosis is a major debilitating cause of fractures and decreases the quality of life in elderly patients. Bone homeostasis is maintained by bone forming osteoblasts and bone resorpting osteoclasts. Substantial evidences have shown that targeting osteoclasts using natural products is a promising strategy for the treatment of osteoporosis. In the current study, we investigated the osteoprotective effect of Abietic acid (AA) in in vitro and in vivo models of osteolysis. In vitro experiments demonstrated that, AA suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and F-actin ring formation in a concentration dependent manner. Mechanistically, AA abrogated RANKL-induced phosphorylation of IKKα/β (ser 176/180), IkBα (ser 32), and inhibited the nuclear translocation of NF-κB. We also found that, AA attenuated the RANKL-induced phosphorylation of MAPKs and decreased the expression of osteoclast specific genes such as TRAP, DC-STAMP, c-Fos, and NFATc1. Consistent with in vitro results, in vivo Lipoploysaccharide (LPS)-induced osteolysis model showed that AA inhibited the LPS-induced serum surge in cytokines TNF-α and IL-6. μ-CT analysis showed that AA prevented the LPS-induced osteolysis. Furthermore, histopathology and TRAP staining results suggested that AA decreased the number of osteoclasts in LPS-injected mice. Taken together, we demonstrated that the osteoprotective action of AA is coupled with the inhibition of NF-κB and MAPK signaling and subsequent inhibition of NFATc1 and c-Fos activities. Hence, AA may be considered as a promising drug candidate for the treatment of osteoporosis.
- Published
- 2017
29. Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats†
- Author
-
Shankar Ganesh Gadepalli, Ramakrishna Sistla, Madhusudana Kuncha, Bidya Dhar Sahu, and Vegi Ganga Modi Naidu
- Subjects
Male ,Curcumin ,Necrosis ,Prednisolone ,Freund's Adjuvant ,Interleukin-1beta ,Pharmaceutical Science ,Arthritis ,Pharmacology ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,medicine ,Animals ,Rats, Wistar ,Plant Extracts ,Tumor Necrosis Factor-alpha ,business.industry ,Body Weight ,medicine.disease ,Arthritis, Experimental ,Rats ,Drug Combinations ,chemistry ,Freund's adjuvant ,Toxicity ,Steroids ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Spleen ,Oxidative stress ,medicine.drug - Abstract
Objectives The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Methods Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Key findings Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Conclusion Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis.
- Published
- 2013
30. Synthesis and anticancer activity of some new s-triazine derivatives
- Author
-
Shweta Shrivastava, Vegi Ganga Modi Naidu, G. Jagadeesh Kumar, Kolupula Srinivas, H. V. S. Sriramkumar Bomma, E. Srihari, and V. Jayathirtha Rao
- Subjects
Colorectal cancer ,Stereochemistry ,Organic Chemistry ,medicine.disease ,In vitro ,chemistry.chemical_compound ,Breast cancer ,chemistry ,Cancer cell ,medicine ,Potency ,General Pharmacology, Toxicology and Pharmaceutics ,Lung cancer ,Ovarian cancer ,Triazine - Abstract
New s-triazine derivatives 13a–h were synthesized for the structure–activity relationship studies as potent anticancer agents. The prepared analogues were evaluated for their in vitro inhibitory activity against the growth of PA-1 (Ovarian cancer), A549 (Lung cancer), MCF-7 (Breast cancer), and HT-29 (Colon cancer). Tri-substituted s-triazine derivatives (13e–h) with morpholino group on s-triazine scaffold exhibited potent anticancer activities compared to di-substituted s-triazine derivatives. Compounds 13e–h also showed relatively selective PA-1 and HT-29 cancer cell inhibition over other cancer cell lines. Structure–activity relationships provided useful insights in these classes of compounds and paved the way to design novel analogues with more potency.
- Published
- 2013
31. Fast dissolving drug-drug eutectics with improved compressibility and synergistic effects
- Author
-
Vegi Ganga Modi Naidu, Rahul B. Chavan, Dinesh Thumuri, Nalini R. Shastri, and Rajesh Thipparaboina
- Subjects
Drug ,Cancer chemotherapy ,Stereochemistry ,media_common.quotation_subject ,Pharmaceutical Science ,02 engineering and technology ,Synergistic combination ,010402 general chemistry ,01 natural sciences ,Cell Line ,Mice ,Propranolol Hydrochloride ,Cell Line, Tumor ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Etodolac ,Dissolution ,Chromatography, High Pressure Liquid ,Eutectic system ,media_common ,Acetaminophen ,Chemistry ,Drug Synergism ,021001 nanoscience & nanotechnology ,Propranolol ,0104 chemical sciences ,Solubility ,Dose reduction ,Inflammation Mediators ,0210 nano-technology ,Powder Diffraction ,medicine.drug ,Nuclear chemistry - Abstract
Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties. A 6 to 9 fold enhancement in % dissolution efficiency was found at 1min suggesting the fast dissolving capabilities of the eutectic mixtures when compared to plain drug. In addition, eutectic mixtures have shown improved hardness compared to plain drugs. EP and EPHC have shown around 5 fold and 3 fold improvements in hardness respectively at 10MPa when compared to plain etodolac. Cell culture studies have shown improved effects of EP. Western blotting analysis revealed that the said combination successfully reduced various inflammatory mediators like TNF-α, COX-2 and IL-6. Whereas, the eutectic combination EPHC has shown enhanced cytotoxic effects with synergistic combination index and favorable dose reduction index. The generated multi-component systems EP and EPHC with fast dissolving capabilities, improved hardness at lower pressures and synergistic effects represent prospective combinations for effective treatment of osteoarthritis and cancer chemotherapy respectively.
- Published
- 2016
32. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents
- Author
-
Suresh K. Bhargava, Vegi Ganga Modi Naidu, Niggula Praveen Kumar, Dinesh Thummuri, T. Srinivasa Reddy, Kishna Ram Senwar, Pankaj Sharma, and Nagula Shankaraiah
- Subjects
Cell Survival ,Cell ,Antineoplastic Agents ,Apoptosis ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Cytotoxic T cell ,Humans ,Propidium iodide ,DAPI ,Pharmacology ,A549 cell ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Cell growth ,Organic Chemistry ,Cell Cycle ,General Medicine ,Flow Cytometry ,Molecular biology ,0104 chemical sciences ,Cell biology ,medicine.anatomical_structure ,Cell culture ,A549 Cells ,Benzimidazoles ,Thiazolidinediones - Abstract
A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50 value of 11.46 ± 1.46 μM on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549 cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p.
- Published
- 2016
33. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer
- Author
-
Deep Pooja, Hitesh Kulhari, Shweta Shrivastava, Vegi Ganga Modi Naidu, David J. Adams, Madhusudana Kuncha, Vipul Bansal, and Ramakrishna Sistla
- Subjects
Dendrimers ,Cell Survival ,Receptor, ErbB-2 ,Biocompatible Materials ,Breast Neoplasms ,02 engineering and technology ,Pharmacology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,In vivo ,Dendrimer ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Fluorescein isothiocyanate ,skin and connective tissue diseases ,Cell Proliferation ,Multidisciplinary ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,chemistry ,Docetaxel ,030220 oncology & carcinogenesis ,Cancer cell ,Female ,0210 nano-technology ,Fluorescein-5-isothiocyanate ,medicine.drug - Abstract
Approximately 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2)-positive. This type of breast cancer is more aggressive and tends to reoccur more often than HER2-negative breast cancer. In this study, we synthesized trastuzumab (TZ)-grafted dendrimers to improve delivery of docetaxel (DTX) to HER2-positive breast cancer cells. Bioconjugation of TZ on the surface of dendrimers was performed using a heterocrosslinker, MAL-PEG-NHS. For imaging of cancer cells, dendrimers were also conjugated to fluorescein isothiocyanate. Comparative in vitro studies revealed that these targeted dendrimers were more selective, and had higher antiproliferation activity, towards HER2-positive MDA-MB-453 human breast cancer cells than HER2-negative MDA-MB-231 human breast cancer cells. When compared with unconjugated dendrimers, TZ-conjugated dendrimers also displayed higher cellular internalization and induction of apoptosis against MDA-MB-453 cells. Binding of TZ to the dendrimer surface could help site-specific delivery of DTX and reduce systemic toxicity resulting from its lack of specificity. In addition, in vivo studies revealed that the pharmacokinetic profile of DTX was significantly improved by the conjugated nanosystem.
- Published
- 2016
- Full Text
- View/download PDF
34. Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs
- Author
-
Boyapati Shireesha, Prakash V. Diwan, Banda Narsaiah, Sistla Ramakrishna, Vegi Ganga Modi Naidu, Kuncha Madhusudana, and A. R. Rao
- Subjects
Male ,Thienopyridines ,Thienopyridine ,Indomethacin ,Drug Evaluation, Preclinical ,Arthritis ,Pharmacology ,Cell Line ,Nitric oxide ,Proinflammatory cytokine ,Mice ,chemistry.chemical_compound ,Edema ,Animals ,Medicine ,Stomach Ulcer ,Rats, Wistar ,Granuloma ,business.industry ,Macrophages ,Anti-Inflammatory Agents, Non-Steroidal ,medicine.disease ,Arthritis, Experimental ,Rats ,Carrageenan ,Disease Models, Animal ,Dextran ,chemistry ,Immunology ,Cytokines ,Arachidonic acid ,medicine.symptom ,business - Abstract
The present study was designed to evaluate the anti-inflammatory and antiarthritic activity of the new synthetic thienopyridine analogs. The anti-inflammatory activity of thienopyridines was assayed by using carrageenan; dextran and arachidonic acid induced paw edema models (acute), cotton pellet granuloma model (Sub acute) and Freund's complete adjuvant induced arthritis (chronic) in experimental rats. The compounds BN-4, BN-14 and BN-16 have shown significant inhibition of edema in carrageenan and arachidonic acid induced paw edema model at a dose of 100 mg/kg compared to the dextran induced paw edema model and also showed significant inhibition in granuloma tissue formation and Freund's complete adjuvant induced arthritis in experimental rats. These thienopyridine analogs also inhibited the proinflammatory mediators such as Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Nitric Oxide (NO) in Lipopolysaccharide (LPS) challenged murine macrophages. Ulcerogenecity study results revealed less ulcerogenic potential of BN-4, BN-14 and BN-16 compared to nonsteroidal anti-inflammatory drug (NSAID) indomethacin in rats. In conclusion, the new thienopyridine analogs were promising for the potential use as anti-inflammatory agents for both acute and chronic inflammatory disorders with low toxic effects.
- Published
- 2012
35. Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole-based 2,4-thiazolidinedione derivatives as PPAR-γ modulators
- Author
-
Md. Jahangir Alam, Mohd. Javed Naim, Ozair Alam, Md. Mumtaz Alam, Mohammad Shaquiquzzaman, and Vegi Ganga Modi Naidu
- Subjects
0301 basic medicine ,medicine.drug_class ,Pharmaceutical Science ,Peroxisome proliferator-activated receptor ,Pharmacology ,01 natural sciences ,Streptozocin ,Diabetes Mellitus, Experimental ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,Transactivation ,In vivo ,3T3-L1 Cells ,Drug Discovery ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Thiazolidinedione ,Cells, Cultured ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Biological activity ,Rats ,0104 chemical sciences ,Molecular Docking Simulation ,PPAR gamma ,HEK293 Cells ,030104 developmental biology ,chemistry ,Docking (molecular) ,Pyrazoles ,Thiazolidinediones ,Rosiglitazone ,Pioglitazone ,medicine.drug - Abstract
The design, synthesis, structure-activity relationship, and biological activity of 2,4-thiazolidinedione derivatives as peroxisome proliferator-activated receptor-γ (PPAR-γ) modulators for antidiabetic activity are reported. Fifteen 2,4-thiazolidinedione derivatives clubbed with pyrazole moiety were docked into the ligand binding domain of PPAR-γ by the Glide XP module of Schrodinger. Eight derivatives (5a, 5b, 5d, 5f, 5i, 5l, 5n, 5o) having Glide XP scores > -8 as compared to the standard drug, rosiglitazone (Glide XP score = -9.165), showed almost similar interaction with the amino acids such as HIS 449, TYR 473, TYR 327, HIS 323, and SER 289 in the molecular docking studies. These eight derivatives were further screened for PPAR-γ transactivation and in vivo blood glucose lowering activity in the streptozotocin-induced diabetic rat model. Compounds 5o, 5n, 5a, 5i, and 5b showed 52.06, 51.30, 48.65, 43.13, and 40.36% PPAR-γ transactivation as compared to the reference drugs rosiglitazone and pioglitazone with 85.30 and 65.22% transactivation, respectively. The data analysis showed significant blood glucose lowering effects (hypoglycemia) of compounds 5o, 5n, and 5a (140.1 ± 4.36, 141.4 ± 6.15, and 150.7 ± 4.15, respectively), along with reference drugs pioglitazone (135.2 ± 4.91) and rosiglitazone (141.1 ± 5.88) as compared to the diabetic control. Furthermore, the most potent compound 5o also elevated the PPAR-γ gene expression by 2.35-fold as compared to rosiglitazone (1.27-fold) and pioglitazone (1.6-fold). It also significantly lowered the AST, ALT, and ALP levels and caused no damage to the liver.
- Published
- 2018
36. Anti-Amnesic Activity of Vitex Negundo in Scopolamine Induced Amnesia in Rats
- Author
-
Vegi Ganga Modi Naidu, Abhinav Kanwal, Yogendra Kumar Gupta, Jogender Mehla, Madhusudana Kuncha, and Ramakrishna Sistla
- Subjects
Vitex negundo ,Antioxidant ,biology ,Aché ,business.industry ,medicine.medical_treatment ,Amnesia ,Glutathione ,Pharmacology ,Avoidance response ,biology.organism_classification ,medicine.disease_cause ,language.human_language ,Toxicology ,chemistry.chemical_compound ,chemistry ,language ,Medicine ,medicine.symptom ,business ,Donepezil ,Oxidative stress ,medicine.drug - Abstract
In the present study we investigated the anti-amnesic activity of Vitex negundo in scopolamine induced amnesia in rats. Wistar rats (180-200 g) were trained on active avoidance task. Each animal received session of 15 trials with inter trial duration of 15 s for 5 days. Scopolamine (3 mg/kg, i.p) was administered at different time periods on the basis of stages of memory i.e acquisition, consolidation and retention in different groups (n = 6). Effect of Vitex negundo extract was evaluated and compared to a standard drug, Donepezil. Significant (p < 0.05) increase in the avoidance response on the 5th session has been observed as compared to 1st session in control group. Scopolamine treatment significantly (p < 0.05) reduced the avoidance response compared to control. Extract treated groups shown significant (p < 0.05) increase in number of avoidance responses as compared to scopolamine treated groups. Increased oxidative stress in brain after scopolamine treatment, as observed by increase in MDA & decrease in GSH & SOD, was lowered in the groups treated with extracts. AChE activity was also improved after V. negundo treatment. Results of the study have shown that V. negundo treated groups decrease the phenomenon of amnesia by increasing learning of memory through antioxidant effect and decreasing AChE activity.
- Published
- 2010
37. First stereoselective total synthesis and anticancer activity of new amide alkaloids of roots of pepper
- Author
-
Ch. Naveen Kumar, Prakash V. Diwan, Vegi Ganga Modi Naidu, B. China Raju, Sistla Ramakrishna, V. Jayathirtha Rao, and Ch. Srinivas
- Subjects
Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Stereoisomerism ,Plant Roots ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Alkaloids ,Piperidines ,Cell Line, Tumor ,Amide ,Drug Discovery ,Humans ,Organic chemistry ,Molecular Biology ,Organic Chemistry ,Total synthesis ,Piperaceae ,Amides ,chemistry ,Wittig reaction ,Molecular Medicine ,Epimer ,Stereoselectivity ,Drug Screening Assays, Antitumor ,Sharpless asymmetric dihydroxylation - Abstract
The first stereoselective total synthesis of new natural amide alkaloids 1-3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a trans regioselective opening of 2,3-epoxy alcohol, Horner-Wadsworth-Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids 1-3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time.
- Published
- 2009
38. Polyelectrolyte complexes of gum kondagogu and chitosan, as diclofenac carriers
- Author
-
Koppolu Madhusudhana, Roop K. Khar, R.B. Sashidhar, Vegi Ganga Modi Naidu, Sistla Ramakrishna, Farhan Jalees Ahmed, and Prakash V. Diwan
- Subjects
Polymers and Plastics ,Stereochemistry ,Organic Chemistry ,Diclofenac Sodium ,Natural gum ,Polyelectrolyte ,Bioavailability ,Chitosan ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,Zeta potential ,medicine ,Swelling ,medicine.symptom ,Drug carrier ,Nuclear chemistry - Abstract
Polyelectrolyte complexes (PEC) of gum kondagogu (GKG) and chitosan were prepared by mixing polymeric solutions of different concentrations (0.02–0.18% w/v). The complex formed were loaded with diclofenac sodium, and the release of the drug was measured in vitro and in vivo, along with the measurement of particle size, zeta potential, complex formation, flow properties, and loading efficiency. Maximum yield of PEC was observed at gum kondagogu concentrations above 80%. The PEC showed lower release of diclofenac sodium in 0.1 N HCl as compared to phosphate buffer (pH 6.8). Increasing the concentration of gum kondagogu in PEC led to an increase in drug release. However, PEC 1:3 (gum kondagogu: chitosan) with higher concentration of chitosan showed 98% release with in 4.5 h, owing to the fact that chitosan has a higher degree of swelling in acidic medium. PEC 5:1 and 3:1 showed a 5.3- and 5.8-fold increase in relative bioavailability compared to the free drug when administered orally to the rats.
- Published
- 2009
39. Pyrrolo[2,1-c][1,4]benzodiazepine-β-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies
- Author
-
Ramakrishna Sistla, P. Raju, Vegi Ganga Modi Naidu, Venkatesh Tekumalla, Prakash V. Diwan, and Ahmed Kamal
- Subjects
Alkylating Agents ,Stereochemistry ,Clinical Biochemistry ,Nitro compound ,Mice, Nude ,Pharmaceutical Science ,Pyrrolobenzodiazepine ,Antineoplastic Agents ,Chorionic Gonadotropin ,Biochemistry ,Chemical synthesis ,Mice ,chemistry.chemical_compound ,Glucuronides ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Prodrugs ,Cytotoxicity ,Molecular Biology ,chemistry.chemical_classification ,Benzodiazepinones ,Organic Chemistry ,Water ,Adept ,gamma-Glutamyl Hydrolase ,Prodrug ,Kinetics ,Enzyme ,Solubility ,chemistry ,Molecular Medicine ,Glucuronide ,Neoplasm Transplantation - Abstract
Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs 15a-b, with a potential for selective therapy of solid tumors by PMT and ADEPT have been designed, synthesized and evaluated for selective cytotoxicity in the presence of the enzyme beta-glucuronidase. The prodrugs have been found to possess reduced cytotoxicity compared to the parent moieties, and are excellent substrates for the enzyme, exhibiting cytotoxicity selectively in the presence of the enzyme. Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs.
- Published
- 2008
40. Evaluation of antimicrobial, antioxidant and wound-healing potentials of Holoptelea integrifolia
- Author
-
Vegi Ganga Modi Naidu, Sistla Ramakrishna, Boreddy Srinivas Reddy, R. Kiran Kumar Reddy, Sachin B. Agwane, Prakash V. Diwan, and Koppolu Madhusudhana
- Subjects
Male ,Antioxidant ,Free Radicals ,DPPH ,medicine.medical_treatment ,Microbial Sensitivity Tests ,Pharmacognosy ,Antioxidants ,Inhibitory Concentration 50 ,Minimum inhibitory concentration ,Hydroxyproline ,chemistry.chemical_compound ,Anti-Infective Agents ,Drug Discovery ,medicine ,Animals ,Agar diffusion test ,Rats, Wistar ,Urticaceae ,Pharmacology ,Wound Healing ,Bacteria ,Traditional medicine ,Plant Extracts ,Fungi ,Antimicrobial ,Rats ,Plant Leaves ,Disease Models, Animal ,Biochemistry ,chemistry ,Plant Bark ,Reactive Oxygen Species ,Wound healing - Abstract
The methanolic extracts of Holoptelea integrifolia (Roxb.) (Urticaceae) leaves (MLE) and stem bark (MSBE) were studied for the wound-healing potential. Since wound healing is severely hampered by microbial infection and reactive oxygen species (ROS), this study was undertaken to evaluate antimicrobial and antioxidant activity apart from wound-healing activity. The antimicrobial property of the Holoptelea was studied against the six bacterial and five fungal strains using the agar well diffusion method and minimum microbicidal concentration and minimum inhibitory concentration were determined for each strain, in which methanolic extract of stem bark (MSBE) has shown bigger zone of inhibition (11.3-20.4 mm) than methanolic extract of leaves (MLE) (9.6-14.9 mm). The anti-oxidant activity was evaluated by DPPH free radical scavenging activity using HPLC method. The IC(50) values obtained for MSBE (TPC: 78.53+/-1.26 mg/g) and MLE (TPC: 57.71+/-1.45 mg/g) were 37.66+/-0.48 and 50.36+/-0.59 microg/well, respectively. In excision wound model, more than 90% wound healing was recorded in treated groups by 14 days of post surgery, where as only 62.99% was observed in the control group. In incision model, higher breaking strengths and higher hydroxyproline content in treated groups suggested higher collagen re-deposition than the control group. Finally, histopathology studies conformed wound-healing activity of Holoptelea integrifolia.
- Published
- 2008
41. Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity, DNA-binding ability, viscosity and molecular modeling studies
- Author
-
Chetna Jadala, Narayana Nagesh, Vegi Ganga Modi Naidu, Nagula Shankaraiah, Shweta Shrivastava, Shalini Nekkanti, Kishna Ram Senwar, Manda Sathish, and Ahmed Kamal
- Subjects
Circular dichroism ,Molecular model ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Harmine ,Cell Line, Tumor ,Drug Discovery ,Humans ,Cytotoxicity ,Molecular Biology ,IC50 ,010405 organic chemistry ,Viscosity ,Circular Dichroism ,Organic Chemistry ,DNA ,Triazoles ,Combinatorial chemistry ,0104 chemical sciences ,Molecular Docking Simulation ,chemistry ,Cell culture ,Click chemistry ,Carbolines - Abstract
A series of new DNA-interactive C3-tethered 1,2,3-triazolo-β-carboline derivatives have been synthesized via 'click' reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. Interestingly, these hybrids have displayed potent in vitro cytotoxicity in comparison to Harmine against the HT-29 (colon cancer) and HGC-27 (gastric cancer) cell lines. The compounds 7f, 7k, 7n and 7s appear to be more effective against the HGC-27 cell line, among which compound 7f showed the highest cytotoxicity (5.44 ± 0.58, IC50 μM). The compounds 7e and 7f appear to be more active against the HT-29 cell line, among which compound 7f exhibited the highest cytotoxicity (3.67 ± 0.62, IC50 μM). To gain more insight into the DNA-binding ability, spectroscopic techniques such as UV-Visible, fluorescence and circular dichroism studies were performed. Viscosity measurements and molecular docking studies substantiate that these compounds indeed bind to DNA via the minor groove.
- Published
- 2015
42. H2O-mediated isatin spiro-epoxide ring opening with NaCN: Synthesis of novel 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids and their anticancer evaluation
- Author
-
Vegi Ganga Modi Naidu, Nagula Shankaraiah, Ahmed Kamal, Manish Kumar Jeengar, Pankaj Sharma, T. Srinivasa Reddy, and Kishna Ram Senwar
- Subjects
Isatin ,Indoles ,Tetrazoles ,Antineoplastic Agents ,Apoptosis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Sodium Cyanide ,Drug Discovery ,Humans ,Spiro Compounds ,Cytotoxicity ,Sodium cyanide ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Cell growth ,Organic Chemistry ,Acridine orange ,Water ,General Medicine ,Oxindoles ,Biochemistry ,Cell culture ,DNA fragmentation ,Epoxy Compounds ,Drug Screening Assays, Antitumor ,Ethidium bromide ,Reactive Oxygen Species - Abstract
A simple method for isatin spiro-epoxide ring-opening by sodium cyanide in water to obtain a variety of isatin hydroxy nitriles has been developed. Further, these intermediates have been converted into new 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids via azide-nitrile cycloaddition reaction in a sealed tube. These compounds were evaluated for their in vitro anticancer activity on five human cancer cell lines i.e. breast (BT549 and MDA MB-231), prostate (PC-3 and DU-145) and ovarian (PA-1). The compounds 6d and 6r showed potent anticancer activity against DU-145 cell line with IC50 values in the range of 7.01 ± 0.91 and 4.26 ± 0.09 μM respectively. The compounds 6d, 6g, 6q and 6r were also tested on human normal prostate epithelial (RWPE-1) cells and found to be safer with lesser cytotoxicity. The morphology and long term clonogenic survival of DU-145 cells were severely affected by compound 6r. Cell cycle analysis revealed that the compounds arrest the cells in G2/M phase. Acridine orange/ethidium bromide (AO/EB) staining, DAPI staining, annexin-V binding assay and DNA fragmentation analysis showed that cell proliferation was inhibited through induction of apoptosis. Moreover, one of the compounds 6r treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) in DU-145 cells.
- Published
- 2015
43. Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling
- Author
-
Vegi Ganga Modi Naidu, Manish Kumar Jeengar, Dinesh Thummuri, Ravindar Naik Ramavat, Shweta Shrivastava, Harishankar Nemani, and Pradip Chaudhari
- Subjects
musculoskeletal diseases ,Lipopolysaccharides ,Male ,Osteolysis ,Lipopolysaccharide ,MAP Kinase Signaling System ,Osteoclasts ,Inflammation ,IκB kinase ,Pharmacology ,Bone resorption ,chemistry.chemical_compound ,Mice ,Osteoclast ,medicine ,Benzoquinones ,Animals ,Phosphorylation ,Thymoquinone ,biology ,Chemistry ,RANK Ligand ,NF-kappa B ,3T3 Cells ,medicine.disease ,Mice, Inbred C57BL ,Oxidative Stress ,medicine.anatomical_structure ,RAW 264.7 Cells ,RANKL ,biology.protein ,Cancer research ,medicine.symptom - Abstract
Osteoclasts are multinuclear giant cells responsible for bone resorption in inflammatory bone diseases such as osteoporosis, rheumatoid arthritis and periodontitis. Because of deleterious side effects with currently available drugs the search continues for novel effective and safe therapies. Thymoquinone (TQ), the major bioactive component of Nigella sativa has been investigated for its anti-inflammatory, antioxidant and anticancer activities. However, its effects in osteoclastogenesis have not been reported. In the present study we show for the first time that TQ inhibits nuclear factor-KB ligand (RANKL) induced osteoclastogenesis in RAW 264.7 and primary bone marrow derived macrophages (BMMs) cells. RANKL induced osteoclastogenesis is associated with increased expression of multiple transcription factors via activation of NF-KB, MAPKs signalling and reactive oxygen species (ROS). Mechanistically TQ blocked the RANKL induced NF-KB activation by attenuating the phosphorylation of IkB kinase (IKKα/β). Interestingly, in RAW 264.7 cells TQ inhibited the RANKL induced phosphorylation of MAPKs and mRNA expression of osteoclastic specific genes such as TRAP, DC-STAMP, NFATc1 and c-Fos. In addition, TQ also decreased the RANKL stimulated ROS generation in macropahges (RAW 264.7) and H2O2 induced ROS generation in osteoblasts (MC-3T3-E1). Consistent with in vitro results, TQ inhibited lipopolysaccharide (LPS) induced bone resorption by suppressing the osteoclastogenesis. Indeed, micro-CT analysis showed that bone mineral density (BMD) and bone architecture parameters were positively modulated by TQ. Taken together our data demonstrate that TQ has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-KB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.
- Published
- 2015
44. Design, synthesis and anticancer evaluation of tetrahydro-β-carboline-hydantoin hybrids
- Author
-
Pankaj Sharma, Vunnam Srinivasulu, Kishna Ram Senwar, Karmarajsinh J. Chudasama, Gannoju Srinivasulu, Vegi Ganga Modi Naidu, Ahmed Kamal, Manish Kumar Jeengar, Nagula Shankaraiah, and Shalini Nekkanti
- Subjects
Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Hydantoin ,Antineoplastic Agents ,Biochemistry ,HeLa ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Structure–activity relationship ,Humans ,MTT assay ,Cytotoxicity ,Molecular Biology ,Etoposide ,Cell Proliferation ,biology ,Chemistry ,Hydantoins ,Organic Chemistry ,biology.organism_classification ,Mechanism of action ,Cell culture ,Molecular Medicine ,medicine.symptom ,Drug Screening Assays, Antitumor ,medicine.drug ,Carbolines - Abstract
A series of new tetrahydro-β-carboline-hydantoin hybrids have been designed and synthesized based on the structure of the known Eg5 inhibitor HR22C16. These compounds have been evaluated for their anticancer activity against lung (A549), cervical (ME180, HeLa), prostate (PC-3) and breast (MCF-7) cancer cell lines by MTT assay. These hybrids have displayed significant in vitro cytotoxicity in comparison to etoposide against PC-3, A549, and MCF-7 cell lines. The hybrids 3a, 3b, 3c, 3e, 3f, 3g, 4b, 4c, 4e and 4f appear to be more effective against the PC-3 cell line, among which compound 4b displayed the highest cytotoxicity (6.08 ± 0.2, IC₅₀ μM). Based on these results, an attempt was made to rationalize their mechanism of action through cell cycle analysis studies. The flow-cytometric analysis of compound 4b in PC-3 cells indicated a G2/M cell cycle arrest. Molecular docking studies substantiate that these compounds indeed bind to the allosteric site of Eg5 formed from Glu116, Gly117, Glu118, Trp127, Ala133, Ile136, Pro137, Tyr211, Leu214, and Glu215 residues with the most potent compound 4b showing the most favorable interaction.
- Published
- 2014
45. A new sesquiterpene lactone from the roots of Saussurea lappa: Structure–anticancer activity study
- Author
-
Eppakayala Sreedhar, P.V. Srinivas, Sistla Rama Krishna, Vegi Ganga Modi Naidu, K. Suresh Babu, J. Madhusudana Rao, A. Robinson, and T. Vijay Kumar
- Subjects
Saussurea ,Germacranolide ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Chemistry, Pharmaceutical ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Pharmacognosy ,Sesquiterpene lactone ,Sesquiterpene ,Plant Roots ,Biochemistry ,Mass Spectrometry ,Inhibitory Concentration 50 ,Lactones ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Molecular Biology ,Saussurea lappa ,chemistry.chemical_classification ,Costunolide ,Plant Extracts ,Organic Chemistry ,Stereoisomerism ,chemistry ,Epidermoid carcinoma ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Sesquiterpenes ,Lactone - Abstract
The dried roots of Saussurea lappa, called costus roots, are used in the traditional system of medicine for the treatment of cancer. In our investigation for the anticancer constituents from the hexane extract of this plant, a new sesquiterpene (1) was isolated along with the known compounds costunolide (2), beta-cyclocostunolide (3), dihydro costunolide (4) and dehydro costuslactone (5). Their structures were established by the extensive spectroscopic analyses. In addition, costunolide and beta-cyclocostunolide derivatives were synthesized using Michael-type addition reaction of NaOMe to the alpha-methylene-gamma-lactone moiety. All the compounds were tested for their in vitro cytotoxic activity. Compound 1 exhibited potent cytotoxic activity and other compounds displayed moderate activity.
- Published
- 2008
46. Antioxidant and hepatoprotective effects of Boswellia ovalifoliolata bark extracts
- Author
-
Rajeswara Rao Pragada, Ramakrishna Sistla, Bandari Uma Mahesh, Shweta Shrivastava, and Vegi Ganga Modi Naidu
- Subjects
Male ,Antioxidant ,medicine.medical_treatment ,Pharmacology ,medicine.disease_cause ,Antioxidants ,Lipid peroxidation ,chemistry.chemical_compound ,Liver Function Tests ,Picrates ,Lactate dehydrogenase ,Drug Discovery ,medicine ,Animals ,Boswellia ,Rats, Wistar ,Transaminases ,Acetaminophen ,chemistry.chemical_classification ,Reactive oxygen species ,L-Lactate Dehydrogenase ,Plant Extracts ,Biphenyl Compounds ,General Medicine ,Glutathione ,Alkaline Phosphatase ,Oxidative Stress ,Complementary and alternative medicine ,chemistry ,Hepatoprotection ,Biochemistry ,Liver ,Toxicity ,Plant Bark ,Lipid Peroxidation ,Chemical and Drug Induced Liver Injury ,Oxidative stress ,Phytotherapy - Abstract
Paracetamol (PCM) hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata (BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.
- Published
- 2013
47. ChemInform Abstract: Synthesis and Biological Evaluation of Conformationally Flexible as well as Restricted Dimers of Monastrol and Related Dihydropyrimidones
- Author
-
Sistla Ramakrishna, Vegi Ganga Modi Naidu, M. V. P. S. Vishnuwardhan, Ahmed Kamal, Shaik Azeeza, Shaikh Faazil, M. Shaheer Malik, and Shaik Bajee
- Subjects
chemistry.chemical_classification ,Degree of unsaturation ,chemistry.chemical_compound ,Monastrol ,Chemistry ,General Medicine ,Combinatorial chemistry ,Alkyl ,Biological evaluation - Abstract
The one-pot Biginelli multi-component cyclocondensation reaction affords dimers of monastrol and related dihydropyrimidones with flexible alkyl chain spacers of varying length and conformationally restricted spacers with unsaturation.
- Published
- 2011
48. Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones
- Author
-
Vegi Ganga Modi Naidu, M. V. P. S. Vishnuwardhan, Ahmed Kamal, Shaik Bajee, Shaik Azeeza, Shaikh Faazil, M. Shaheer Malik, and Sistla Ramakrishna
- Subjects
Differential Thermal Analysis ,Lung Neoplasms ,Skin Neoplasms ,Stereochemistry ,Dimer ,Biginelli reaction ,Molecular Conformation ,Antineoplastic Agents ,Breast Neoplasms ,Microbial Sensitivity Tests ,Pyrimidinones ,Gram-Positive Bacteria ,Chemical synthesis ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,Anti-Infective Agents ,Cell Line, Tumor ,Drug Discovery ,Gram-Negative Bacteria ,Structure–activity relationship ,Humans ,Pharmacology ,Organic Chemistry ,Thiones ,Biological activity ,General Medicine ,DNA ,Monastrol ,Pyrimidines ,chemistry ,Epidermoid carcinoma ,Colonic Neoplasms ,Female ,Drug Screening Assays, Antitumor ,Dimerization - Abstract
A series of conformationally flexible and restricted dimers of monastrol as well as related dihydropyrimidones have been synthesized by employing one-pot Biginelli multicomponent reaction. These dimers have been evaluated for cytotoxic potency against selected human cancer cell lines and some of the compounds have exhibited more cytotoxic potency than the parent monastrol. Further, the DNA binding ability by thermal denaturation studies and antimicrobial activities of these compounds are also discussed.
- Published
- 2010
49. ChemInform Abstract: First Stereoselective Total Synthesis and Anticancer Activity of New Amide Alkaloids of Roots of Pepper
- Author
-
Ch. Srinivas, Vegi Ganga Modi Naidu, Ch. Naveen Kumar, V. Jayathirtha Rao, Sistla Ramakrishna, Prakash V. Diwan, and B. China Raju
- Subjects
chemistry.chemical_compound ,Chemistry ,Stereochemistry ,Amide ,Wittig reaction ,Pepper ,Total synthesis ,Regioselectivity ,Stereoselectivity ,Alcohol ,General Medicine ,Sharpless asymmetric dihydroxylation - Abstract
The first stereoselective total synthesis of new natural amide alkaloids 1-3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a trans regioselective opening of 2,3-epoxy alcohol, Horner-Wadsworth-Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids 1-3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time.
- Published
- 2010
50. ChemInform Abstract: Bioactivity-Guided Isolation of Cytotoxic Constituents from Stem-Bark of Premna tomentosa
- Author
-
S. Rama Krishna, A. Hymavathi, J. Madhusudana Rao, Vegi Ganga Modi Naidu, K. Suresh Babu, and Prakash V. Diwan
- Subjects
Betulin ,biology ,Stereochemistry ,Premna ,General Medicine ,Fractionation ,biology.organism_classification ,Syringaldehyde ,Terpene ,chemistry.chemical_compound ,chemistry ,Diterpene ,Two-dimensional nuclear magnetic resonance spectroscopy ,Lupeol - Abstract
A bioassay-guided fractionation and chemical investigation of the stem bark of Premna tomentosa resulted in the isolation and characterization of four new icetexane diterpenes (1-4), along with the known compounds coniferaldehyde (5), syringaldehyde (6), lupeol (7), betulin (8), and 2-(4-methoxyphenyl)-2-butanone (9). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. The new compounds exhibited diverse functionalities on a common icetexane diterpene skeleton. In addition, cytotoxic activities of the icetexanes (1-3) were evaluated by determining their inhibitory effects on the human cancer cell lines (MCF-7, HT-29, Hep-G2, A-431, and A-549). Compounds 1 and 3 showed selective inhibitory activity against MCF-7 (15.96microg/mL and 15.84microg/mL) and HT-29 cell lines (16.21microg/mL and 14.57microg/mL), respectively.
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.