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Zika virus infection causes significant congenital disabilities, in addition to microcephaly while an excited mother is infected during pregnancy. Mosquito vectors are the main spreaders of the zika virus which includes Aedes albopictus and Aedes aegypti. presently clear-cut and definite treatment for the zika virus is not yet available. engrossing in silico approach present study determines the active fighter constituents from aboriginal antiviral herbs to regulate the zika virus. The Lipinski rule filter was used for the Phytoconstituents to determine their molecular interactions and pharmacokinetic studies. NS5 polymerase protein (PDB ID; 5U04) and ligand interactions were determined using Schrodinger Maestro software version 12.7. The outcome displayed that Quercetin, Moupinamide, Epigallocatechin gallate, and Myricetin have sharpened synergism with the asparte active site of NS5 RdRps with docking score (-6.087, -5.838, - 5.812, -5.418 Kcal/mol). Analysing the pharmacokinetic study hydrogen bonds with 2.5 Å for target Aspartate amino acid have prime activity. the present study propounds that Quercetin can be used as an inhibitor of the Zika virus. [ABSTRACT FROM AUTHOR]

A series of 1-(substitutedbenzylidene)-4-(4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl) phenyl)semicarbazide derivatives were synthesized with the aim of developing potential antimicrobials. It was characterized by FT-IR, 1H NMR, Mass spectroscopy and elemental analysis. In addition, the in vitro antibacterial and antifungal properties were tested against some human pathogenic microorganisms by employing the disc diffusion technique and agar streak dilution method. All title compounds showed activity against the entire strain of microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. Based on the results obtained, compound 5j was found to be very active compared to the rest of the compounds which were subjected to antimicrobial assay.

A series of 1-(4-substitutedphenyl)-3-phenyl-1H-pyrazole-4-carbaldehydes 4a–l have been synthesized and tested for their biological activities. Formation of the pyrazole derivatives was achieved by treating with Vilsmeier-Haack reagent. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to Diclofenac sodium as standard drug. Compounds 4g, 4i and 4k exhibited the maximum anti-inflammatory and analgesic activities. The detailed synthesis, spectroscopic and toxicity data are reported.

A variety of novel isatin derivatives 5a–5j and 6a–6j were synthesized and characterized by spectroscopic means and elemental analysis. The title compounds were investigated for antiepileptic activity using MES and scPTZ seizures tests. Neurotoxicity study was performed by the rotorod test. The relationship between the functional group variation and the biological activity of the evaluated compounds was discussed. Among the synthesized analogs, the most active one was 6f that revealed protection in MES at a dose of 30 mg/kg (i.p.) after 0.5 h and 4 h. This molecule also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).

A series of novel N-((1H-benzoimidazol-1-yl) methyl)-4-(1-phenyl-5-substituted-4, 5-dihydro-1-benzoimidazol-1-yl) methyl)-4-(1-phenyl-5-substituted-4, 5-dihydro-1H-pyrazol-3-yl) benzenamine were synthesized by treating various 1-(4-((1H-benzoimidazol-1-yl) methylamino) phenyl)-3-substitutedprop-2-en-1-one with phenyl hydrazine in the presence of sodium acetate through a simple ring closure reaction. The starting material, 1-(4-((1H-benzoimidazol-1-yl) methylamino) phenyl)-3-substitutedprop-2-en-1-one,-benzoimidazol-1-yl) methylamino) phenyl)-3-substitutedprop-2-en-1-one, was synthesized from o-phenylenediamine by a multistep synthesis. All the synthesized compounds were characterized by spectroscopic means and elemental analyses. The title compounds were investigated for in vitro antibacterial and antifungal properties against some human pathogenic microorganisms by employing the agar streak dilution method using Ciprofloxacin and Ketoconazole as standard drugs. All title compounds showed activity against the entire strains of microorganism. Structural activity relationship studies reveal that compounds possessing an electron-withdrawing group display better activity than the compounds containing electron-donating groups, whereas the unsubstituted derivatives display moderate activity. Based on the results obtained, N-((1H-benzoimidazol-1-yl) methyl)-4-(1-phenyl-5-(4-(trifluoromethyl) phenyl)-4,5-dihydro-1H-pyrazol-3-yl) benzenamine 5i was found to be very active compared with the rest of the compounds and standard drugs that were subjected to antimicrobial assay.

In the present study, novel Schiff bases were synthesized by condensation of 3-amino-2-methyl quinazolin-4-(3H)-ones with different aromatic aldehydes. The 3-amino-2-methyl quinazolin-4-(3H)-one was synthesized from anthranilic acid via the 2-methyl benzoxazin-4-one. The chemical structures of the synthesized compounds were confirmed by means of Infrared (IR), 1 H-NMR, 13 C-NMR, Mass spectral, and Elemental analysis. These compounds were screened for anti-bacterial (Staphylococcus aureus ATCC 9144, Staphylococcus epidermidis ATCC 155, Micrococcus luteus ATCC 4698, Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, and Klebsiella pneumoniae ATCC 11298)) and anti-fungal (Aspergillus niger ATCC 9029 and Aspergillus fumigatus ATCC 46645) activities, using the paper disk diffusion technique. The minimum inhibitory concentrations (MIC) of the compounds were also determined by the agar streak dilution method. Most of the synthesized compounds exhibited significant anti-bacterial and anti-fungal activities. Among the synthesized compounds, 3-(4-hydroxy benzylideneamino)-2-methyl quinazolin-4(3H)-one 4g and 4c was found to exhibit the highest anti-bacterial activity and 3-(4-hydroxy-3-methoxy benzylideneamino)-2-methyl quinazolin-4(3H)-one 4k exhibited the highest anti-fungal activity.

Enhanced cancer treatment remains as one of the focused areas for researchers around the world. Hence, the progress in this direction will be a challenge and an opportunity in, inter‐disciplinary field to mitigate the suffering of millions in the upcoming decades. As we see, cancer death rate has also progressively increased despite the current impressive treatment regimens but also due to the non‐availability of vaccines and the re‐occurring of cancer in substantially recovered patients. Currently, numerous treatment strategies like surgical removal of solid tumors followed by radiation with a combination of immunotherapy/chemotherapy by the researchers and clinicians are routinely being followed. However, recurrence and distant metastasis often occur following radiation therapy, commonly due to the generation of radio‐resistance through deregulation of the cell cycle, cell death, and inhibition of DNA damage repair mechanisms. Thus, chemotherapeutic/immunotherapeutic treatment systems have progressed remarkably in the latest years owing to destroying tumors, noninvasive, and affordable charge of therapy. But, traditional chemotherapeutic approaches target the DNA of mutated and normal healthy cells, resulting in a significantly increased risk of toxicity and drug resistance. Thus, many receptors targeted therapies are in the developmental phase of discovery. Cancer cells have a specialized set of surface receptors that provide potential targets for cancer therapeutics. Cell surface receptor‐dependent endocytosis is well a known major mechanism for the internalization of macromolecular drugs. This review emphasizes the recent development of several surface receptors mediated cancer‐targeting approaches for the effective delivery of various therapeutic formulations. [ABSTRACT FROM AUTHOR]

Context: Cancer is a complex neoplastic disorder. Globally, it is said to be the second leading cause of death. Aim: The aim of the present study was to assess the prescribing pattern, adverse drug reactions, potential drug-drug interactions and psychological distress in cancer patients. Settings and Design: A prospective observational study was carried out on 65 cancer patients for 6 months at Erode Cancer Centre. Methods and Material: A socio-demographic questionnaire, Naranjo's and Hartwig's scales to evaluate the probability and severity of adverse drug reactions and Depression, Anxiety and Stress Scale 21 for psychological distress were used. Potential Drug-Drug Interactions were examined by Micromedex®. Statistical analysis used: Descriptive analysis was performed and outcomes were presented in percentage. Results: Most of the study participants had carcinoma cervix 10(15.3%). The most frequently prescribed anticancer drug was cisplatin 48(73.8%). Cyclophosphamide + doxorubicin 6(46.1%) was found mostly of the 13 PDDIs identified. ADRs were commonly experienced with mucositis 18(25%), alopecia 11(15.2%) and vomiting 10(13.8%). 63(87.5%) were probable ADRs and 54(75%) were found to be moderate in severity. The overall psychological distress showed 70.7% depression, 77% anxiety and 66.1% stress. Conclusion: To prevent morbidity and mortality among cancer patients, due consideration should be provided to monitor the rational use of drugs. Proper screening of PDDIs and spontaneous reporting of ADRs can be emphasized by health care professionals with psychosocial care. [ABSTRACT FROM AUTHOR]

Background: Injuries are neglected significant public health problem worldwide which; requires organized efforts for prevention. The vehicle population of India constitutes only 1 percent of the world but accounts for nearly 10% of the total accidents in the world. Globalization has led to increased vehicular movements leading to unsafe roads. Materials and Method: This study aims at providing, comparison between Tamil Nadu and Kerala on the basis of Injury rates, on type of vehicle involved, type of roads and causative factor leading to road traffic crashes. In order to understand the severity of accidents and trends over time, we have collected data from various state and national reports published on various forums regarding the accidents in India, Tamil Nadu and Kerala and analyzed the data to see the trends and number of injuries over the past 3 years. Results: Between the two states, Tamil Nadu has shown high injury rates comparatively to Kerala over the period of 3 years. Though there are measures in place, somewhere there is a lack in proactive measure to stop this modern epidemic of motor vehicle trauma which shows an increase in accidents in Tamil Nadu than in Kerala. [ABSTRACT FROM AUTHOR]

In the present investigation, solid lipid nanoparticles (SLNs)-loaded in situ gel with voriconazole drug was formulated. Further, the formulation was characterized for pH, gelling capacity, entrapment efficiency, in vitro drug release, drug content, and viscosity. Voriconazole is an antifungal drug used to treat various infections caused by yeast or other types of fungi. Film hydration technique was used to prepared SLNs from lecithin and cholesterol. Based on the entrapment efficiency 67.2-97.3% and drug release, the optimized formulation NF1 of SLNs was incorporated into in situ gels. The in situ gels were prepared using viscosity-enhancing polymers such as Carbopol and (hydroxypropyl) methyl cellulose (HPMC). Formulated SLN in situ gel formulations were characterized, which showed pH 4.9-7.1, drug content 65.69-96.3% and viscosity (100 rpm) 120-620 cps. From the characterizations given above, F6 was optimized and evaluated for microbial assay and ocular irritation studies. Microbial assay was conducted by the cup-plate method using Candida albicans as the test organism. An ocular irritation study was conducted on albino rabbits. The results revealed that there was no ocular damage to the cornea, conjunctiva, or iris. Stability studies were carried out on the F6 formulation for 3 months, which showed that the formulation had good stability. These results indicate that the studied SLNs-loaded in situ gel is a promising vehicle for ocular delivery. [ABSTRACT FROM AUTHOR]

The following study was done to assess the glucose utilizing efficiency of Indoloquinoxaline derivative incorporated keratin nanoparticles (NPs) in 3T3‐L1 adipocytes. Indoloquinoxaline derivative had wide range of biological activities including antidiabetic activity. In this view, Indoloquinoxaline moiety containing N, N‐dimethyl (3‐fluoro‐6H‐indolo [3,2‐b] quinoxalin‐6‐yl) methanamine compound was designed and synthesized, and further it is incorporated into keratin nanoparticles. The formulated NPs, drug entrapment efficiency, releasing capacity, stability, and physicochemical properties were characterized by various spectral analyzer and obtained results of characterizations were confirmed the properties of NPs. The analysis of mechanism underlying the glucose utilization of NPs was examined through molecular docking with identified target, and observed in silico study reports shown strong interaction of NPs in the binding pockets of AMPK and PTP1B. Based on the in silico screening, the formulated NPs was performed for in vitro cellular viability and glucose uptake studies on 3T3‐L1 adipocytes. Interestingly, 40 μg of NPs displayed 78.2 ± 2.76% cellular viability, and no cell death was observed at lower concentrations. Further, the concentration dependent glucose utilization was observed at different concentrations of NPs in 3T3‐L1 adipocytes. The results of NPs (40 μg) on glucose utilization have revealed eminent result 58.56 ± 4.54% compared to that of Metformin (10 μM) and Insulin (10 μM). The identified results clearly indicated that Indoloquinoxaline derivative incorporated keratin NPs significantly increased glucose utilization efficiency and protect the cells against the insulin resistance. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) speeds up the drug development process and reduces its time, as well as the cost which is of enormous importance in outbreaks such as COVID-19. It uses a set of machine learning algorithms that collects the available data from resources, categorises, processes and develops novel learning methodologies. Virtual screening is a successful application of AI, which is used in screening huge drug-like databases and filtering to a small number of compounds. The brain's thinking of AI is its neural networking which uses techniques such as Convoluted Neural Network (CNN), Recursive Neural Network (RNN) or Generative Adversial Neural Network (GANN). The application ranges from small molecule drug discovery to the development of vaccines. In the present review article, we discussed various techniques of drug design, structure and ligand-based, pharmacokinetics and toxicity prediction using AI. The rapid phase of discovery is the need of the hour and AI is a targeted approach to achieve this., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: We synthesized a series of novel amide derivatives of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine [5a-5r] and assessed for their antiproliferative activity against human breast cancer cell line MCF7 by using MTT assay. Graph Theoretical analysis, in silico modeling, molecular dynamic studies, and ADME profile were screened for the synthesized compounds. Based on the observed report, the significant compounds were chosen for their anticancer activity. Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substitutedphenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer., Methods: 5-((2-chloropyridin-4-yl)oxy) (2-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1- (4-substituted phenyl) -N,N-dimethylethen-1-amine [5a-5r] was synthesized using 2-bromo-1-phenylethanone and (5-(2-chloropyridin-4-yloxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylmethanamine with different aromatic aldehydes and their characterization studies were evaluated by IR, NMR, and mass spectral analysis., Results: The compound 2-(4-methylphenyl)-1-(5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5a and 2-(2-methylphenyl)-1-(5-((2-chloro pyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5c in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 3.3 mM for MCF-7 cells, and produced dramatic cell cycle arrest at EGFR phase as an indicator of apoptotic cell death induction., Conclusion: Based on their high potency in the cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess the potential to design more potent compounds for intervention with cancer cell proliferation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μg ml -1 IC 50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.

Objective: Site-specific and toxic-free drug delivery, is an interesting area of research. Nanoengineered drug delivery systems possess a remarkable potential for effective treatment of various types of cancers., Methods: In this study, novel Folic Acid (FA) conjugated keratin nanoparticles (NPs) were assembled with encapsulation and delivery of Rutin (Rt) into breast cancer cells through the overexpressed folate receptor. The biocompatible, Rt encapsulated FA conjugated keratin NPs (FA@Ker NPs) were successfully formulated by a modified precipitation technique. Their morphological shape and size, size distribution, stability, and physical nature were characterized and confirmed. The drug (Rt) encapsulation efficiency, loading capacity and release kinetics were also studied., Results: The observed results of molecular docking and density functionality theory of active drug (Rt) showed a strong interaction and non-covalent binding of the folate receptor and facilitation of endocytosis in breast cancer cells. Further, in vitro cytotoxic effect of FA@Ker NPs was screened against MCF-7 cancer cells, at 55.2 µg/mL of NPs and found to display 50% of cell death at 24h. Moreover, the NPs enhanced the uptake of Rt in MCF-7 cells, and the apoptotic effect of condensed nuclei and distorted membrane bodies was observed. Also, NPs entered into the mitochondria of MCF-7 cells and significantly increased the level of ROS which led to cell death., Conclusion: The developed FA@Ker NPs might be a promising way to enhance anti-cancer activity without disturbing normal healthy cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the present study, a series of novel Schiff bases of isatin [5a-5l] were synthesized by condensation of imesatin with different aromatic aldehydes. The imesatins were synthesized by the reaction of isatin with p-phenylenediamine. The chemical structures of the synthesized compounds were confirmed by means of Infrared (IR), Mass spectroscopy, and Elemental analysis. These compounds were screened for the analgesic activity by the tail-immersion method at a dose of 200 mg/kg body weight. Among the tested compounds 3-(4-(4-hydroxy-3-methoxylbenzylideneamino) phenylimino) indoline-2-one (5i) exhibited better analgesic activity when compared to standard pentazocine. From the above-mentioned results it may be concluded that compounds containing electron-donating groups exhibit better analgesic activity than the electron-withdrawing groups.