41 results on '"Chawla, Pooja"'
Search Results
2. Approaches to the Treatment of Pulmonary Obstruction: The Role of Nano-Biomaterials in Therapeutic Targeting
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Diksha, Ranjan, Animesh, Kaur, Simran Deep, Komal, Mathur, Harshita, Yadav, Gaurav, Panda, Brajesh Kumar, Patil, Niraj, John, Okesanya Olalekan, Singh, Amandeep, Chawla, Viney, Chawla, Pooja A., Pradhan, Madhulika, editor, Yadav, Krishna, editor, and Singh Chauhan, Nagendra, editor
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- 2024
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3. Stratagems for Breast Cancer Management in the Era of Nanotheranostics
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Goel, Honey, Arora, Pankaj, Riya, Chawla, Viney, Singla, Richu, Chawla, Pooja A., Barkat, Md. Abul, editor, Ahmad, Farhan Jalees, editor, Rahman, Mohammad Akhlaquer, editor, and Ansari, Mohammad Azam, editor
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- 2024
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4. Exploring the Role of ADME for Anticancer Prodrugs
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Virendra, Sharma Arvind, Chawla, Pooja A., Singh, Shamsher, Kumar, Anil, Section editor, Kumar, Deepak, Section editor, Sobti, R. C., editor, Ganguly, Nirmal K., editor, and Kumar, Rakesh, editor
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- 2024
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5. Advancements in ulcerative colitis management: A critical assessment of etrasimod therapy
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Seni, Kushal, Saini, Aniket, Debnath, Rabin, Singh, Arshdeep, Sharma, Anjali, Bisht, Deepak Singh, Chawla, Viney, and Chawla, Pooja A
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- 2024
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6. Unravelling the genomic maze: Bioinformatics unleashes insights into Sotos syndrome (Cerebral Gigantism)
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Sharma, Ravinder, Kaur, Simarjeet, Gupta, Vikas, Grover, Harpreet, Yadav, Kiran, Chawla, Viney, and Chawla, Pooja A
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- 2024
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7. Cipaglucosidase alfa-atga: Unveiling new horizons in Pompe disease therapy
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Singh, Arshdeep, Debnath, Rabin, Saini, Aniket, Seni, Kushal, Sharma, Anjali, Bisht, Deepak Singh, Chawla, Viney, and Chawla, Pooja A
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- 2024
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8. Unlocking InhA: Novel approaches to inhibit Mycobacterium tuberculosis
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Wahan, Simranpreet K., Bhargava, Gaurav, Chawla, Viney, and Chawla, Pooja A.
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- 2024
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9. Exploration of oxadiazole clubbed benzhydrylpiperazine pharmacophoric features as structural feature for antidepressant activity: In vitro, in vivo and in silico analysis
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Kumar Nandi, Nilay, Das, Shibam, Choudhary, Diksha, Saini, Suresh, Bhatia, Rohit, Chawla, Pooja, Kaur, Rajwinder, Kalra, Sourav, Rawat, Ravi, Eyupoglu, Volkan, and Kumar, Bhupinder
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- 2024
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10. Harnessing click chemistry for the discovery of fluorescent materials
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Wahan, Simranpreet K., Bhargava, Gaurav, and Chawla, Pooja A.
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- 2024
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11. Surface plasmon resonance as a fascinating approach in target-based drug discovery and development
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Das, Shibam, Singh, Sukhwinder, Chawla, Viney, Chawla, Pooja A., and Bhatia, Rohit
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- 2024
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12. Recent Developments in the Antimicrobial Potential of Some Nitrogenous Heterocycles and their SAR Studies: A Review
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Nehra, Bhupender, primary, Kumar, Manoj, additional, Singh, Sumitra, additional, Chawla, Viney, additional, A. Chawla, Pooja, additional, and Grover, Parul, additional
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- 2024
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13. Diastereo- and π-Facially Selective Hetero-Diels Alder Cycloaddition Reactions of 3-Butadienyl-2-Azetidinones with Diazo-Dienophiles.
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Mann, Maninderjeet Kaur, Sharma, Rashmi, Chawla, Pooja, Kumar, Rupesh, and Bhargava, Gaurav
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RING formation (Chemistry) ,ALDER - Abstract
The reported work presents the diastereo, regio-, and π-facial selective synthesis of hetero-Diels-Alder (H-DA) cycloadducts with diazene derivatives viz. di-isopropyldiazocarboxylate and diethylazodicarboxylate with cis-/trans-3-butadienyl-β-lactams having stereocentres at its α and β-position. The H-DA reactions resulted in the formation of β-lactam tethered—3,6-dihydro-pyridazines in good yields. [ABSTRACT FROM AUTHOR]
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- 2024
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14. A Computational Study on the Structural Prediction of InhA Inhibitors as Antimycobacterial Agents.
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Wahan, Simranpreet K., Pathania, Shelly, Chawla, Pooja A., and Bhargava, Gaurav
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MOLECULES ,MYCOBACTERIUM tuberculosis ,MOLECULAR docking ,MYCOLIC acids ,DYNAMIC simulation - Abstract
InhA is an enoyl acyl carrier reductase that catalyzes the chemo-selective reduction of its 2-trans-enoyl-ACP substrate. The pharmacological effects of the frontline medications used in the treatment of tuberculosis are elicited by inhibiting the enzyme InhA, which disrupts the mycolic acid biosynthesis pathway. The present study involves development of ligand-based pharmacophore model, docking studies, generation of 3D-QSAR model, and molecular dynamic simulation studies of virtually screened putative InhA inhibitors. The best field-based 3D-QSAR model was validated using partial least-square regression (PLS) method with high regression coefficient for training set (R
2 ) = 0.9256 and test set (R2 ) = 0.7542, cross-validated coefficient (rcv 2 ) = 0.72 and R2 pred = 0.9764. Also, virtual screening yielded compounds 4, 25, 1, and 30 exhibiting appreciable interactions (docking scores −5.972, −3.819, −3.801, and −3.701, respectively with InhA synthetase; PDB ID: 1BVR). Further, ADMET studies supported drug-like potential of compounds 25, 1, and 30 whereas compound 4 showed negligible human oral absorption. The molecular dynamic simulation studies of the top scored molecule 25 suggested stability of 25-1BVR complex over the course of simulation run. Therefore, this work can be helpful for future discovery of novel InhA inhibitors against drug-resistant tuberculosis. [ABSTRACT FROM AUTHOR]- Published
- 2024
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15. Bioactive Flavonoids: A Comprehensive Review on Pharmacokinetics and Analytical Aspects.
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Billowria, Koushal, Ali, Rouchan, Rangra, Naresh Kumar, Kumar, Ram, and Chawla, Pooja A.
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CORONARY disease ,FUNCTIONAL groups ,MORPHOLOGY ,FLAVONOIDS ,HYDROXYL group - Abstract
Flavonoids are a diversified group of natural substances which were discovered to provide a variety of health benefits in human beings. Vegetables, fruits, wine and tea are the primary flavonoid dietary sources for humans and as the flavonoids are so closely connected to human dietary items and health, it is vital to explore the structural-activity connection. The arrangement, replacement of functional groups, and total number of hydroxyl groups around flavonoid's nucleus structure affect their biological activity, metabolism, and bioavailability. Various flavonoids have been proven to have hepatoprotective properties, that help in the prevention of coronary heart disease. Similarly, these flavonoids also possess anticancer, and anti-inflammatory activities. Flavonoids have been found to have a functional and structural link with their enzyme inhibitory action, that appears to have antiviral effect through acting as antioxidants, damaging cell membranes, blocking enzymes, activating mechanisms of host self-defense, and limiting virus penetration and attaching to cells. Identification, characterization, isolation, and biological role of flavonoids, as well as their uses on health advantages, are all major topics in research and development currently. This review represents a summary of various sources of flavonoids, class, subclass, their chemical structures, biological activities, the pharmacokinetics of flavonoids and various analytical, bioanalytical and electrochemical methods for determination of flavonoids from different matrices. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Therapeutic Potential of Natural Metabolites Coupled Pyrazole and Its Bio‐Isosteres: Medicinal Perspectives and SAR Studies
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Nehra, Bhupender, primary, Kumar, Manoj, additional, Chawla, Pooja A., additional, and Chawla, Viney, additional
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- 2024
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17. Looking at the Bright Future of Health Sciences Review
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Chawla, Pooja A., primary and Ekser, Burcin, additional
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- 2024
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18. An insight into recent updates on analytical techniques for bioactive alkaloids
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Saini, Aniket, primary, Seni, Kushal, additional, Chawla, Pooja A., additional, Chawla, Viney, additional, and Ganti, Subrahmanya S., additional
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- 2024
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19. Solid self-nanoemulsifying drug delivery systems of nimodipine: development and evaluation.
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Kumar, Mohit, Chawla, Pooja A., Faruk, Abdul, and Chawla, Viney
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DRUG delivery systems , *TERNARY phase diagrams , *DRUG solubility , *SPRAY drying , *DRUG interactions - Abstract
Background: This study aimed to formulate solid self-nanoemulsifying drug delivery systems (SNEDDS) for nimodipine (NIM). The selection of Cremophor RH 40, Lipoxol 300, and PEG 400 as oil, surfactant, and co-surfactant was based on solubility and self-emulsification assessments. A ternary phase diagram determined the optimal oil to Smix (surfactant/co-surfactant) ratio (40:60). By utilizing liquid SNEDDS (NIM-SNEDDS) as an adsorbate and chitosan EDTA microparticles, developed through spray drying (SD-CHEM) and solvent evaporation (SE-CHEM) as adsorbents, the solid SNEDDS were created (NIM-SD-SSNEDDS and NIM-SE-SSNEDDS, respectively). Results: Both solid formulations exhibited favourable drug loading (NIM-SD-SSNEDDS = 79.67 ± 2.97%, NIM-SE-SSNEDDS = 77.76 ± 4.29%), excellent flowability, and drug amorphization as per XRD and DSC analysis. Scanning electron microscopy revealed smoothening and filling of adsorbent surfaces by adsorbate (with size range NIM-SD-SSNEDDS = 10–15 μm, NIM-SE-SSNEDDS = 20–25 μm). FTIR confirmed no interaction of drug and excipients. Stability studies demonstrated the physical and thermodynamic stability of reconstituted nanoemulsions with droplet size, PDI, zeta potential, emulsification time, % transmittance and cloud temperature for NIM-SD-SSNEDDS as 247.1 nm, PDI 0.620, 1.353 mV, 38–41 s, 94.64%, 54 °C and for NIM-SE-SSNEDDS as 399.6 nm, PDI 0.821, 1.351 mV, 40–48 s, 92.96%, 49 °C, respectively. FE-SEM images showed globules formed with small sizes, and there was no coalescence evidence, implying the reconstituted nanoemulsions' stability. In vitro dissolution studies revealed a fourfold increase in drug dissolution for NIM-SD-SSNEDDS (84.43%) and NIM-SE-SSNEDDS (76.68%) compared to pure drug (28%). Ex vivo permeation studies indicated almost similar profiles for NIM-SD-SSNEDDS (22.61%) and NIM-SE-SSNEDDS (21.93%) compared to NIM-SNEDDS (25.02%). Conclusion: NIM-SD-SSNEDDS exhibited superior performance compared to NIM-SE-SSNEDDS, highlighting the efficacy of microparticles developed by the spray drying method (SD-CHEM) as adsorbents for solidification. These results suggest enhanced dissolution and permeation for nimodipine in both the solid SNEDDS. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Deep learning unlocks label-free viability assessment of cancer spheroids in microfluidics.
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Chun-Cheng Chiang, Anne, Rajiv, Chawla, Pooja, Shaw, Rachel M., He, Sarah, Rock, Edwin C., Mengli Zhou, Jinxiong Cheng, Yi-Nan Gong, and Yu-Chih Chen
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DEEP learning ,MICROFLUIDICS ,DRUG efficacy ,CELL lines ,CELL culture ,HIGH throughput screening (Drug development) - Abstract
Despite recent advances in cancer treatment, refining therapeutic agents remains a critical task for oncologists. Precise evaluation of drug effectiveness necessitates the use of 3D cell culture instead of traditional 2D monolayers. Microfluidic platforms have enabled high-throughput drug screening with 3D models, but current viability assays for 3D cancer spheroids have limitations in reliability and cytotoxicity. This study introduces a deep learning model for non-destructive, label-free viability estimation based on phasecontrast images, providing a cost-effective, high-throughput solution for continuous spheroid monitoring in microfluidics. Microfluidic technology facilitated the creation of a high-throughput cancer spheroid platform with approximately 12000 spheroids per chip for drug screening. Validation involved tests with eight conventional chemotherapeutic drugs, revealing a strong correlation between viability assessed via LIVE/DEAD staining and phase-contrast morphology. Extending the model's application to novel compounds and cell lines not in the training dataset yielded promising results, implying the potential for a universal viability estimation model. Experiments with an alternative microscopy setup supported the model's transferability across different laboratories. Using this method, we also tracked the dynamic changes in spheroid viability during the course of drug administration. In summary, this research integrates a robust platform with highthroughput microfluidic cancer spheroid assays and deep learning-based viability estimation, with broad applicability to various cell lines, compounds, and research settings. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Heterocyclic compounds as xanthine oxidase inhibitors for the management of hyperuricemia: synthetic strategies, structure–activity relationship and molecular docking studies (2018–2024).
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Singh, Arshdeep, Debnath, Rabin, Chawla, Viney, and Chawla, Pooja A.
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- 2024
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22. Deep Learning Unlocks Label-Free Viability Assessment of Cancer Spheroids in Microfluidics
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Chiang, Chun-Cheng, primary, Anne, Rajiv, additional, Chawla, Pooja, additional, Shaw, Rachel M., additional, He, Sarah, additional, Rock, Edwin C., additional, Zhou, Mengli, additional, Cheng, Jinxiong, additional, Gong, Yi-Nan, additional, and Chen, Yu-Chih, additional
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- 2024
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23. An overview of sports-mediated brain injuries and their management approaches: a narrative review.
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GROVER, PARUL, NOBARI, HADI, BHARDWAJ, MONIKA, MEHTA, LOVEKESH, KAPOOR, GARIMA, CHAWLA, POOJA A., and ARDIGÒ, LUCA PAOLO
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BRAIN injuries ,PHARMACOLOGY ,HOSPITALS ,SKATEBOARDING ,CYCLING - Abstract
Purpose. The objective of the present study was to provide an update on the 16 sports with the highest incidence of brain injuries. Thereafter, its diagnosis, treatment, and management strategies are discussed. Methods: The manuscript addresses the brain-related injuries individually in each of the 16 sports with the highest incidence. To simplify the reading, the mentioned 16 sports are sorted alphabetically. A subpart mentioning the management of brainrelated sports injuries, including pharmacological management, is also included in the manuscript. Results: The incidence of sports-mediated brain injuries within hospital-based studies ranged between 3.5 and 31.5 per 100,000. One community-based study using multiple case ascertainment sources identified a higher incidence of 170 per 100,000. Brain injuries due to sports total 1.2-30.3% of all TBIs (traumatic brain injuries). Men have a higher prevalence than women (75.6% vs. 66.1%), and adolescents and young adults had the highest incidence of sports-mediated brain injuries. Almost 50% of head injuries reported during the practice of sports or recreational activities occur in bicycling, skateboarding, or skating incidents. More than 775,000 children, aged 14 and younger, are treated yearly in hospital emergency rooms for sports-related injuries. Conclusions: Brain injuries are common in sports and difficult to manage, but athlete health and injury prevention should be the priority. Preventive measures should be stricter in sports with a higher incidence of brain injury. As for treatment, a comprehensive approach should be adopted. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis.
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Saini, Aniket and Chawla, Pooja A.
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AMYOTROPHIC lateral sclerosis , *LITERATURE reviews , *MUSCLE weakness , *MOTOR neurons , *SPINAL cord - Abstract
Background and purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease‐modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease. Methods: We carried out a literature survey using PubMed, Scopus, National Institutes of Health, and Biogen for articles published in the English language concerned with "amyotrophic lateral sclerosis", pathophysiology, current treatment, treatment under clinical trial, and the newly approved drug "tofersen" and its detailed summary. Results: A comprehensive review of the literature on the pathophysiology, available treatment, and newly approved drug for this condition revealed convincing evidence that we are now able to better monitor and treat ALS. Conclusions: Although treatment of ALS is difficult, the newly approved drug tofersen has emerged as a potential therapy to slow down the progression of ALS by targeting SOD1 mRNA, representing a significant advancement in the treatment of ALS. [ABSTRACT FROM AUTHOR]
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- 2024
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25. MOLECULAR FIELD ANALYSIS AND DYNAMIC SIMULATION STUDIES OF 1,5-DISUBSTITUTED PYRAZOLINE-BASED MAO-A INHIBITORS FOR THE MANAGEMENT OF DEPRESSION.
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Shome, Abhimannu, Chawla, Pooja A., Rangra, Naresh K., Eyupoglu, Volkan, and Rawat, Ravi
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DYNAMIC simulation , *QSAR models , *HYDROGEN bonding interactions , *MENTAL depression , *MOLECULAR docking - Abstract
Depression, along with grief and anxiety, is currently one of the most common mental illnesses. It was placed 25th among the major diseases. QSAR (CoMFA) of 37 compounds with MAO-A inhibitory activity yielded the most significant QSAR model, m.3, with r²= 0.963, SDEC= 0.129, q² = 0.742, SDEP= 0.34. Using the lead likeness matrix, thirty-seven 1,5-disubstituted MAO-A inhibitors were developed and tested based on the QSAR models. The top 13 compounds were identified. Furthermore, compound 2B (ΔG: -10.3 kcal mol-1, RMSD: 0.151 Å) was selected among the top 13 hits obtained from molecular docking experiments. Significant interactions were also observed, including π-π contacts with Phe208, Tyr444, Trp407, and hydrogen bond interactions with Ala68 and Tyr69. Furthermore, dynamic modelling demonstrated that compound 2B (0.11 nm) has higher overall stability than clorgyline, with a lower RMSD value, and may reach equilibrium in the final 20-25 ns. In terms of RMSF, 2B produced around 0.34 nm with less variation than clorgyline. Throughout the simulation, 2B (No. of H-bond: 6) had more hydrogen bonding than clorgyline (No. of H-bond: 3) with the highest occupancy, i.e. 117.39% for GLU216, 29% for TYR444, and 49% for PRO72, and so on. Compound 2B was proven to be the most essential throughout the experiments. These new chemicals will be optimized in vitro and in vivo in the future. This study will surely contribute to the development of novel MAO-A inhibitors for the treatment of depression. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Mapping COVID-19 in India: Southern states at the forefront of new JN.1 variant.
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Debnath, Rabin, Singh, Arshdeep, Seni, Kushal, Sharma, Anjali, Chawla, Viney, and Chawla, Pooja
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- 2024
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27. mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration
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Eder, Ian, Yu, Virginia, Antonello, Jacob, Chen, Fangyuan, Gau, David, Chawla, Pooja, Joy, Marion, Lucas, Peter C., Boone, David, Lee, Adrian V., and Roy, Partha
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Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type versus functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF's interaction is critical for MRTF-A-induced promotion of both two-dimensional and three-dimensional cell migration, while the SAP-domain function is important selectively for three-dimensional cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF's interaction with MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF–SRF gene signature in pair-matched distant metastases versus primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human BC, justifying future development of specific small molecule inhibitors of the MRTF-SRF transcriptional complex as potential therapeutic agents in BC.
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- 2024
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28. LIVING WITH THE GHOST: CAN WE EVER ESCAPE COVID-19'S SHADOW?
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Chawla, Pooja A.
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MENTAL health services , *SCHIFF bases , *BOOSTER vaccines , *PANDEMIC preparedness , *FEVER , *SCHIFF base derivatives - Abstract
An editorial is presented on the enduring impact of COVID-19 and the need for continued adaptation and preparedness. Topics include the emergence of new variants such as JN.1, pharmaceutical responses including vaccine development and repurposing drugs, and strategies for long-term pandemic management such as vaccination campaigns, healthcare enhancement, and global collaboration.
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- 2024
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29. Resilience Against Resistance: Exploring Cutting-edge Therapies for Methicillin-resistant Staphylococcus aureus (MRSA).
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Sharma R, Gupta V, Parashar B, Chawla V, and Chawla PA
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Methicillin-resistant Staphylococcus aureus [MRSA] stands as an enduring threat within healthcare landscapes, characterized by its ability to rapidly evolve and develop resistance to conventional antibiotics. This comprehensive review embarks on a journey through the historical landscape of MRSA, elucidating its initial emergence and subsequent evolution of resistance mechanisms over time. The narrative unfolds to underscore the profound impact of MRSA on patient outcomes and healthcare systems globally. Current trends in MRSA therapies come under meticulous scrutiny, spotlighting the limitations and challenges associated with existing treatment modalities. This analysis underscores the critical need for transformative and innovative therapeutic strategies to effectively combat the ever-growing spectre of drug resistance in MRSA from the exploration of novel antibiotics designed to overcome resistance mechanisms to the promising potential of phage therapy and immunotherapies. Amidst the exploration of innovative therapies, the review identifies and discusses emerging issues and challenges in MRSA management. Insights are provided into the intricate web of obstacles hindering the adoption and implementation of new therapeutic strategies. Furthermore, the socio-economic implications of MRSA and drug resistance are brought to the forefront, emphasizing the broader impact on public health and healthcare systems. In parallel, historical perspectives on MRSA research illuminate key milestones in scientific understanding and technological advancements. The evolution of research strategies and their impact on our ability to comprehend and combat MRSA is examined, providing context for the current state of the field. In conclusion, this review summarizes major findings and drawing implications for the future of MRSA treatment. Recommendations for further research and clinical practice are outlined, encapsulating a holistic overview of the resilient efforts against resistance in the ongoing battle against MRSA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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30. An Insight into Medicinal Chemistry and SAR Studies of Cholinesterase and BACE-1 Inhibitors for Alzheimer's Disease.
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Shome A, Jha KT, Chahat, Chawla V, and Chawla PA
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Alzheimer's Disease (AD) is a serious neurodegenerative condition that predominantly impacts the cholinergic neurons of the entorhinal cortex and hippocampal regions, playing a critical role in learning, navigation, and brain processing. This paper aims to discuss the three main hypotheses of Alzheimer's disease, focusing on neurotoxicity and neurodegeneration caused by mitochondrial dysfunction and ROS production, particularly analyzing the susceptibility differences between genders. Our comprehensive review focuses on significant findings from the past five years, particularly on Cholinesterase (ChE) and BACE-1 inhibitors. Researchers have conducted a detailed analysis of in vitro, in silico, and in vivo data, incorporating extensive Structure-Activity Relationship (SAR) studies. The reviewed papers have been sourced from platforms, such as Google Scholar, Semantic Scholar, and ClinicalTrials.gov, and have been selected based on their AChE and BACE-1 inhibitory activity and structural motif similarity. The review identifies the most effective compounds targeting ChE and BACE-1, highlighting acridine, dihydropyridine, and thiazole-coumarin hybrids for ChE inhibition, and oxadiazole, benzofuran, and dihydropyrimidinone for BACE-1 inhibition. This demonstrates a diverse array of potent heterocyclic hybrids. The review presents a varied compilation of scaffolds showing promise in treating Alzheimer's disease, highlighting the potential of specific compounds against ChE and BACE-1. Given the critical insights derived from our analysis, we posit that this compilation will substantially contribute to the ongoing efforts to combat neurodegeneration and prolong dementia, underscoring the importance of continuous research in this domain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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31. BBBper: A Machine Learning-based Online Tool for Blood-Brain Barrier (BBB) Permeability Prediction.
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Kumar P, Saini V, Gupta D, Chawla PA, and Kumar A
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Aims: Neuronal disorders have affected more than 15% of the world's population, signifying the importance of continued design and development of drugs that can cross the Blood-Brain Barrier (BBB)., Background: BBB limits the permeability of external compounds by 98% to maintain and regulate brain homeostasis. Hence, BBB permeability prediction is vital to predict the activity of a drug-like substance., Objective: Here, we report about developing BBBper (Blood-Brain Barrier permeability prediction) using machine learning tool., Method: A supervised machine learning-based online tool, based on physicochemical parameters to predict the BBB permeability of given chemical compounds was developed. The user-end webpage was developed in HTML and linked with back-end server by a python script to run user queries and results., Result: BBBper uses a random forest algorithm at the back end, showing 97% accuracy on the external dataset, compared to 70-92% accuracy of currently available web-based BBB permeability prediction tools., Conclusion: The BBBper web tool is freely available at http://bbbper.mdu.ac.in., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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32. Exploring the Potential of Terpenoids as a Possible Treatment for Cancer: Structure-Activity Relationship and Mechanistic Studies.
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Singh A, Debnath R, Sharma A, Saini A, Seni K, Chawla V, and Chawla PA
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Cancer stands as a significant global health challenge due to its mortality rates and the complexities involved in its treatment. Addressing issues, such as metastasis, recurrence, chemoresistance, and treatment-related toxicity, remains pivotal in cancer therapy advancement. Therefore, exploration of novel therapeutic agents has emerged as a priority. As the risk of cancer continues to rise, effective measures must be taken to combat it. One promising approach is to explore natural remedies, such as terpenoids, which have demonstrated anticancer activity. Utilizing terpenoids could aid in the development of potent compounds to fight cancer. By studying the structural makeup of various terpenoid derivatives from previous research, we can identify which structural groups are essential for their anticancer activity. This understanding of the structure-activity relationship is crucial for developing new, effective anticancer agents based on terpenoids. Terpenoids, a diverse class of plant-derived secondary metabolites composed of multiple isoprene units, have garnered attention for their potential anticancer and pharmacological qualities. Some terpenoids exhibit notable anticancer effects by concentrating on several stages of cancer development. They show promise in blocking the initiation of early carcinogenesis by the induction of cell cycle arrest, the inhibition of cancer cell differentiation, and the induction of apoptosis. This study delves into the investigation of specific terpenoids showcasing promising anticancer activity against prevalent malignancies, including breast, colon, ovarian, and lung cancers. The study also explores the relationship between the structure and activity of these compounds, which sheds light on how effective they are against a variety of cancer cell types. The comprehensive discussion centres on elucidating terpenoids with substantial potential for combating diverse cancer types, offering insights into their structural features and promising anticancer mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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33. mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration.
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Eder I, Yu V, Antonello J, Chen F, Gau D, Chawla P, Joy M, Lucas P, Boone D, Lee AV, and Roy P
- Abstract
Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type vs functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF's interaction is critical for MRTF-A-induced promotion of both 2D and 3D cell migration, while the SAP-domain function is important selectively for 3D cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF's interaction of MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases vs primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human breast cancer, justifying future development of a specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer., Significance: Actin cytoskeletal dysregulation gives rise to metastatic dissemination of cancer cells. This study mechanistically investigates the impact of specific functional disruption of MRTF (a transcriptional co-factor of SRF) on breast cancer cell migration.This study establishes a novel mechanism linking mDia2 to MRTF-dependent regulation of cell migration and provides clinical evidence for the association between MRTF activity and increased malignancy in human breast cancer.Findings from these studies justify future exploration of specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer.
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- 2024
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34. Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner.
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Chawla P, Gau D, Chen F, Welling N, Boone D, Taboas J, Lee AV, Galson DL, and Roy P
- Abstract
Bone is a frequent site for breast cancer metastasis. Conditioning of the local tumor microenvironment (TME) through crosstalk between tumor cells and bone resident cells in the metastatic niche is a major driving force for bone colonization of breast cancer cells. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL-induced differentiation of bone marrow-derived macrophages to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that breast cancer cell-secreted factors stimulate RANKL-induced OCL differentiation of BMDMs requiring the function of Myocardin-related transcription factor (MRTF) in tumor cells. This is partly attributed to the critical role of MRTF in maintaining the basal cellular expression of connective tissue growth factor (CTGF), a pro-osteoclastogenic matricellular factor known to promote bone metastasis in human breast cancer. Supporting these in vitro findings, bioinformatics analyses of multiple human breast cancer transcriptome datasets reveal a strong positive correlation between CTGF expression and MRTF gene signature further establishing the relevance of our findings in a human disease context. By Luminex analyses, we show that MRTF depletion in breast cancer cells has a broad impact on OCL-regulatory cell-secreted factors that extends beyond CTGF. These findings, taken together with demonstration of MRTF-dependence for bone colonization breast cancer cells in vivo, suggest that MRTF inhibition could be an effective strategy to diminish OCL formation and skeletal involvement in breast cancer. In summary, this study highlights a novel tumor-extrinsic function of MRTF relevant to breast cancer metastasis.
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- 2024
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35. Journey of Teplizumab: A Promising Drug in the Treatment of Type 1 Diabetes Mellitus.
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Sharma N, Das DD, and Chawla PA
- Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease caused by CD4+ and CD8+ that are activated via CD3+ cells and finally lead to the macrophages destroying the beta cells in the pancreas thereby causing diabetes. The anti-CD3 humanized monoclonal antibody was approved on 17th November 2022 by the United States Food Drug Administration (USFDA) with the name teplizumab and the brand name TZIELD. This is the only approved drug that treats type 1 diabetes (T1D) by delaying the onset of stage 3 in type 1 diabetes (T1D). This review outlines essential features of teplizumab including its brief introduction to its mechanism and other therapies for the treatment and various risks as well as the pharmacokinetics and pharmacodynamics of this disease and the clinical trial reports for the completed and ongoing therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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36. Neutron Activation Analysis: An Excellent Nondestructive Analytical Technique for Trace Metal Analysis.
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Das DD, Sharma N, and Chawla PA
- Subjects
- Neutron Activation Analysis, Humans, Trace Elements analysis, Metals analysis, Metals, Heavy analysis
- Abstract
For proper functioning of the human body, several metals are required in different concentrations but if their concentration slightly elevates, because of any metal-contaminated environment or of other food sources, which leads to high toxicity and different chronic health issues. Different analytical techniques like atomic absorption spectroscopy, X-ray fluorescence, inductively coupled plasma- mass spectroscopy (ICP-MS) and flame atomic absorption spectroscopy are used for metals analysis present in different samples in different fields but nowadays neutron activation analysis (NAA) is preferred over other analytical techniques because it is an efficient, multi-elemental, nondestructive analytical technique having an ultralow minimum detection limit, therefore it can detect heavy metals (HMs) even if at a very trace level parts per billion (ppb) with a quite simple sample preparation technique. This technique is known as "referee technique" because of its accuracy and trustworthiness. There is a widespread use of this technique in biomedical science like in Alzheimer's disease, cancer, arthritis, metabolism study, brain tumor and in many more conditions where metals are actively present. For its typical sample sizes and due to a multitude of additional benefits, it also helps in mapping of pathophysiology of the disease. Besides all, mainly in biomedical science the biological samples can easily be analyzed irrespective of any form. In recent years NAA is preferred over other analytical techniques in several research fields, so this article focuses on the analytical technique, its general principle and recent applications.
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- 2024
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37. Nano-nutraceuticals to Combat Oxidative Stress: Unlocking Newer Paradigms in Adjuvant Therapy.
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Pooja, Pandey M, Kumar T, Goswami H, Kumari R, Kumari S, Jain N, Gorain B, Maurya PK, Chawla V, and Chawla PA
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- Humans, Nanoparticles chemistry, Nanotechnology, Animals, Oxidative Stress drug effects, Antioxidants pharmacology, Antioxidants chemistry, Dietary Supplements
- Abstract
Nutraceuticals are products that provide both nutritional and therapeutic benefits. These compounds can slow the aging process and provide physiological effects shielding individuals from acute and chronic diseases. People's interests have shifted from allopathic to Ayurvedic to nutraceuticals in recent years. These are often common dietary supplements that have drawn customers worldwide because of their high nutritional safety and lack of adverse effects when used for a long time. Although conventional dosage forms, including pills, tablets, and semi-solids, are still available, they nevertheless have poorer bioavailability, less stability, and less effectiveness for targeted delivery of bioactives. The use of effective nanocomplex systems as nano-antioxidants using nanotechnology has become a promising field. Among its many uses, nanotechnology is mostly used to create foods and nutraceuticals that are more bioavailable, less toxic, and more sustainable. Additionally, it has been emphasized how precisely nano-pharmaceuticals for oxidative stress produce the desired effects. These improvements show improved antioxidant delivery to the target region, reduced leakage, and increased targeting precision. The outcomes demonstrated that oxidative stress-related illnesses can be effectively treated by lowering ROS levels with the use of nanonutraceuticals. The major ideas and uses of nano-nutraceuticals for health are outlined in this review, with an emphasis on reducing oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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38. Neuroprotective Effect of Natural Indole and β-carboline Alkaloids against Parkinson's Disease: An Overview.
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Shome A, Chahat, Chawla V, and Chawla PA
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- Humans, Animals, Alkaloids chemistry, Alkaloids pharmacology, Alkaloids therapeutic use, Biological Products pharmacology, Biological Products chemistry, Biological Products therapeutic use, Indoles chemistry, Indoles pharmacology, Indoles therapeutic use, Parkinson Disease drug therapy, Parkinson Disease metabolism, Neuroprotective Agents pharmacology, Neuroprotective Agents chemistry, Neuroprotective Agents therapeutic use, Carbolines chemistry, Carbolines pharmacology, Carbolines therapeutic use
- Abstract
Parkinson's disease (PD) is a devastating neurodegenerative condition that mostly damages dopaminergic neurons in the substantia nigra and impairs human motor function. Males are more likely than females to have PD. There are two main pathways associated with PD: one involves the misfolding of α-synuclein, which causes neurodegeneration, and the other is the catalytic oxidation of dopamine via MAO-B, which produces hydrogen peroxide that can cause mitochondrial damage. Parkin (PRKN), α- synuclein (SNCA), heat shock protein (HSP), and leucine-rich repeat kinase-2 (LRRK2) are some of the target areas for genetic alterations that cause neurodegeneration in Parkinson's disease (PD). Under the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is also important in Parkinson's disease (PD), inhibition of mitochondrial complex 1 results in enhanced ROS generation in neuronal cells. Natural products are still a superior option in the age of synthetic pharmaceuticals because of their lower toxicity and moderate side effects. A promising treatment for PD has been discovered using betacarboline (also known as "β-carboline") and indole alkaloids. However, there are not many studies done on this particular topic. In the herbs containing β-carbolines and indoles, the secondary metabolites and alkaloids, β-carbolines and indoles, have shown neuroprotective and cognitive-enhancing properties. In this review, we have presented results from 18 years of research on the effects of indole and β-carboline alkaloids against oxidative stress and MAO inhibition, two key targets in PD. In the SAR analysis, the activity has been correlated with their unique structural characteristics. This study will undoubtedly aid researchers in looking for new PD treatment options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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39. Alkaloids as Additional Weapons in the Fight against Breast Cancer: A Review.
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Chahat, Jha KT, Bhatia R, and Chawla PA
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- Humans, Female, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Antineoplastic Agents, Phytogenic pharmacology, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic therapeutic use, Animals, Structure-Activity Relationship, Cell Proliferation drug effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Alkaloids chemistry, Alkaloids pharmacology, Alkaloids therapeutic use
- Abstract
Breast carcinoma is among the most frequent cancerous tumour in females around the globe. The major modalities now employed in the therapeutic management of breast cancer include surgeries, chemotherapy, and specialized medicines. Despite their potential to help individuals' problems, they are also associated with many negative impacts. As a result, natural products are increasingly regarded to be a preferable alternative. Alkaloids are essential biochemical substances that can be used to develop new drugs. Numerous alkaloids that originate from natural plants have been shown in vitro and in vivo to have anti-proliferation and anti-metastasis actions on different kinds of carcinoma. According to the data collected in this study, the utilization of alkaloids as anti-tumor medicines appears to be extremely potent; nevertheless, extensive studies and clinical trials are required before utilizing individual alkaloids. In this overview, we provide a detailed and vital exploration of pre-existing alkaloids possessing anti-tumor activities due to bioactive compounds. This study also includes an overview of synthesized analogues and pharmacological characteristics that will be beneficial to scientists working on alkaloids for medicinal purposes. In a recent survey of the literature, alkaloids are an important component of plantderived antitumor medicines that hold great potential for the future development of cancer therapy and preventive therapies. We have also discussed structural analysis relationship (SAR) studies. Moreover, it covers clinical trial medications and FDA-approved medicines from the last five years that will be useful in further research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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40. Mechanistic Study on the Possible Role of Embelin in Treating Neurodegenerative Disorders.
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Anika, Arora R, Virendra SA, and Chawla PA
- Abstract
Embelin (EMB) (2,5-Dihydroxy-3-undecyl-1,4-benzoquinone) is a natural benzoquinone extracted mainly from Embelia ribes (ER) and appear as vivid orange dots beneath the fruit's pericarp. It is being used to treat various diseases since ancient times in India. It has been ascribed as one of the 32 ayurvedic drugs of national importance in the National Medicinal Plant Board set up by the Government of India under the Ministry of Indian System of Medicine and Homeopathy. Embelin prevents neuronal oxidative damage by decreasing the peroxidation of lipids. Along with having antioxidant properties, it also prevents the production of amyloid-protein-related fibrils and blocks the progression of inflammatory cascades. Due to embelin's ability to cross the blood-brain barrier, its neuroprotective effects have been studied in the past using in vitro models of neuronal disorders such as convulsion and epilepsy, Alzheimer's disease, anxiety and depression, traumatic brain injury, cerebral ischemia, Huntington's disease, and multiple sclerosis. In addition to its neuroprotective effects, its role as an antitubercular, anti-cancer, antioxidant, astringent, anti-inflammatory, anti-bacterial, contraceptive, carminative, diuretic, and anthelmintic agent has also been studied. With docking studies and recent advancements in formulations of embelin including polyethylene and embelin micelles and embelin noisome preparations, embelin can prove to be a promising compound for its therapeutic actions in a wide range of diseases and disorders. The findings of docking studies suggest the binding ability of embelin to be similar to the standard drug in their respective disorders. In this review and docking analysis, we bring an outline of scientific evidence concerning the neuroprotective actions of embelin, still, further research is required for its prospective as a chief compound in clinical approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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41. Paradigms and Success Stories of Natural Products in Drug Discovery Against Neurodegenerative Disorders (NDDs).
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Singh S, Chib S, Akhtar MJ, Kumar B, Chawla PA, and Bhatia R
- Subjects
- Humans, Drug Discovery, Biological Products pharmacology, Biological Products therapeutic use, Biological Products chemistry, Neurodegenerative Diseases drug therapy, Parkinson Disease drug therapy, Alzheimer Disease drug therapy
- Abstract
Neurodegenerative disorders (NDDs) are multifaceted complex disorders that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented a great challenge in drug discovery and continuous efforts are in progress in search of suitable therapeutic candidates. Nature has a great wealth of active principles in its lap that has cured the human population since ancient times. Natural products have revealed several benefits over conventional synthetic medications and scientists have shifted their vision towards exploring the therapeutic potentials of natural products in the past few years. The structural mimicking of natural compounds to endogenous ligands has presented them as a potential therapeutic candidate to prevent the development of NDDs. In the presented review, authors have summarized demographical facts about various NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and various types of sclerosis in the brain. The significant findings of new active principles of natural origin along with their therapeutic potentials on NDDs have been included. Also, a description of clinical trials and patents on natural products has been enlisted in this compilation. Although natural products have shown promising success in drug discovery against NDDs, still their use is associated with several ethical issues which need to be solved in the upcoming time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
- Full Text
- View/download PDF
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