Dr Akhil Nagar
@rcpatelpharmacy.co.in
Associate Professor
RCP-IPER
EDUCATION
M. Pharm, Ph D, DDP
RESEARCH INTERESTS
Organometallic chemistry, In silico designing, Organic chemist
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Mithun Rudrapal, Biswatrish Sarkar, Prashanta Kumar Deb, Atul R. Bendale, and Akhil Nagar
Wiley
N. A. Karande, L. G. Rathi, K. S. Kamble, A. Nagar, S. Gholve, A. R. Bendale, K. Danao, and P. D. Bangre
Springer Science and Business Media LLC
Samadhan U. Shinde, , Ruchita S. Bardiya, Pritam S. Jain, Atul A. Shikhedkar, and Akhil A. Nagar
Indian Drug Manufacturers' Association (IDMA)
Forced degradation studies in tablet and bulk formulations of remogliflozin etabonate have been developed using a precise and sensitive high performance thin layer chromatographic method. The silica gel RP-18 F254S plates were used as the stationary phase and ACN: water: ammonia solution (8:2:0.5 V/V/V) was used as the mobile phase for estimation. The proposed method was successfully validated, showing the Rf of the drug as 0.72 at 229 nm. The method was observed to be linear in the range of 500-3000 ng band-1 and then degradation was estimated by forced degradation pathway. In the forced degradation studies, the drug was found to be highly susceptible to both acid and base, including oxidative conditions, providing an active metabolite when remaining in contact in stressed conditions for a short time (30 min), while in longer duration (36 h), the drug provided another metabolite which on characterization was found to be inactive and predicted to be reported in the metabolic pathway
Prashant J. Chaudhari, Sanjaykumar B. Bari, Sanjay J. Surana, Atul A. Shirkhedkar, Chandrakant G. Bonde, Saurabh C. Khadse, Vinod G. Ugale, Akhil A. Nagar, and Rameshwar S. Cheke
American Chemical Society (ACS)
Three crucial anticancer scaffolds, namely indolin-2-one, 1,3,4-thiadiazole, and aziridine, are explored to synthesize virtually screened target molecules based on the c-KIT kinase protein. The stem cell factor receptor c-KIT was selected as target because most U.S. FDA-approved receptor tyrosine kinase inhibitors bearing the indolin-2-one scaffold profoundly inhibit c-KIT. Molecular hybrids of indolin-2-one with 1,3,4-thiadiazole (IIIa–m) and aziridine (VIa and VIc) were afforded through a modified Schiff base green synthesis using β-cyclodextrin-SO3H in water as a recyclable proton-donor catalyst. A computational study found that indolin-2,3-dione forms a supramolecular inclusion complex with β-cyclodextrin-SO3H through noncovalent interactions. A molecular docking study of all the synthesized compounds was executed on the c-KIT kinase domain, and most compounds displayed binding affinities similar to that of Sunitinib. On the basis of the pharmacokinetic significance of the aryl thioether linkage in small molecules, 1,3,4-thiadiazole hybrids (IIIa–m) were extended to a new series of 3-((5-(phenylthio)-1,3,4-thiadiazol-2-yl)imino)indolin-2-ones (IVa–m) via thioetherification using bis(triphenylphosphine)palladium(II)dichloride as the catalyst for C–S bond formation. Target compounds were tested against NCI-60 human cancer cell lines for a single-dose concentration. Among all three series of indolin-2-ones, the majority of compounds demonstrated broad-spectrum activity toward various cancer cell lines. Compounds IVc and VIc were further evaluated for a five-dose anticancer study. Compound IVc showed a potent activity of IC50 = 1.47 μM against a panel of breast cancer cell lines, whereas compound VIc exhibited the highest inhibition for a panel of colon cancer cell lines at IC50 = 1.40 μM. In silico ADME property descriptors of all the target molecules are in an acceptable range. Machine learning algorithms were used to examine the metabolites and phase I and II regioselectivities of compounds IVc and VIc, and the results suggested that these two compounds could be potential leads for the treatment of cancer.
Mithun Rudrapal, Abdul Rashid Issahaku, Clement Agoni, Atul R. Bendale, Akhil Nagar, Mahmoud E. S. Soliman, and Deepak Lokwani
Informa UK Limited
Abstract Due to the unavailability specific drugs or vaccines (FDA approved) that can cure COVID-19, the development of potent antiviral drug candidates/therapeutic molecules against COVID-19 is urgently required. This study was aimed at in silico screening and study of polyphenolic phytochemical compounds in a rational way by virtual screening, molecular docking and molecular dynamics studies against SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) enzymes. The objective of the study was to identify plant-derived polyphenolic compounds and/or flavonoid molecules as possible antiviral agents with protease inhibitory potential against SARS-CoV-2. In this study, we report plant-derived polyphenolic compounds (including flavonoids) as novel protease inhibitors against SARS-CoV-2. From virtual docking and molecular docking study, 31 polyphenolic compounds were identified as active antiviral molecules possessing well-defined binding affinity with acceptable ADMET, toxicity and lead-like or drug-like properties. Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively. Molecular dynamics simulation studies of these compounds in complex with the proteases showed that the binding of the compounds is characterized by structural perturbations of the proteases suggesting their antiviral activities. These compounds can therefore be investigated further by in vivo and in vitro techniques to assess their potential efficacy against SARS-CoV-2 and thus serve as the starting point for the development of potent antiviral agents against the deadly COVID-19. Communicated by Ramaswamy H. Sarma
Akhil Nagar, Chaitali Patel, Pritam Jain, Samadhan Shinde, Atul Shirkhedkar, and Ruchita Bardya
ACG Publications