Publications by authors named "Charu Upadhyay"

4 Publications

  • Page 1 of 1

Multi-targeting approach for nsp3, nsp9, nsp12 and nsp15 proteins of SARS-CoV-2 by Diosmin as illustrated by molecular docking and molecular dynamics simulation methodologies.

Methods 2021 Feb 25. Epub 2021 Feb 25.

Department of Chemistry, Miranda House, University of Delhi, Delhi 110007, India. Electronic address:

Novel coronavirus SARS-CoV-2continues tospread rapidly worldwide and causing serious health and economic loss. In the absence of any effective treatment, various in-silico approaches are being explored towards the therapeutic discovery against COVID-19. Targeting multiple key enzymes of SARS-CoV-2 with a single potential drug could be an important in-silico strategy to tackle the therapeutic emergency. A number of Food and Drug Administration (FDA) approved drugs entered into clinical stages were originated from multi-target approaches with an increased rate, 16-21% between 2015 and 2017. In this study, we selected an FDA-approved library (Prestwick Chemical Library of 1520 compounds) and implemented in-silico virtual screening against multiple protein targets of SARS-CoV-2 on the Glide module of Schrödinger software (release 2020-1). Compounds were analyzed for their docking scores and the top-ranked against each targeted protein were further subjected to Molecular Dynamics (MD) simulations to assess the binding stability of ligand-protein complexes. A multi-targeting approach was optimized that enabled the analysis of several compounds' binding efficiency with more than one protein targets. It was demonstrated that Diosmin (6) showed the highest binding affinity towards multiple targets with binding free energy (kcal/mol) values of -63.39 (nsp3); -62.89 (nsp9); -31.23 (nsp12); and -65.58 (nsp15). Therefore, our results suggests that Diosmin (6) possesses multi-targeting capability, a potent inhibitor of various non-structural proteins of SARS-CoV-2, and thus it deserves further validation experiments before using as a therapeutic against COVID-19 disease.
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http://dx.doi.org/10.1016/j.ymeth.2021.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904494PMC
February 2021

Experimental and Computational Studies of Microwave-Assisted, Facile Ring Opening of Epoxide with Less Reactive Aromatic Amines in Nitromethane.

ACS Omega 2020 Aug 21;5(30):18746-18757. Epub 2020 Jul 21.

Department of Chemistry, Miranda House, University of Delhi, Delhi 110007, India.

Nucleophilic ring opening reactions of epoxides with aromatic amines are in the forefront of the synthetic organic chemistry research to build new bioactive scaffolds. Here, convenient, green, and highly efficient regioselective ring opening reactions of sterically hindered (2,3)-3-(-Boc-amino)-1-oxirane-4-phenylbutane with various poorly reactive aromatic amines are accomplished under microwave irradiation in nitromethane. All the reactions effectively implemented for various aromatic amines involve the reuse of nitromethane that supports its dual role as a solvent and catalyst. The corresponding new β-alcohol analogs of hydroxyethylamine (HEA) are isolated in 41-98% yields. The reactions proceed under mild conditions for a broad range of less reactive and sterically hindered aromatic amines. Proton NMR experiments suggest that the nucleophilicity of amines is influenced by nitromethane, which is substantiated by the extensive computational studies. Overall, this methodology elucidates the first-time use of nitromethane as a solvent for the ring opening reactions under microwave conditions involving an equimolar ratio of epoxide and aromatic amine without any catalyst, facile ring opening of complex epoxide by less reactive aromatic amines, low reaction time, less energy consumption, recycling of the solvent, and simple workup procedures.
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http://dx.doi.org/10.1021/acsomega.0c01760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408245PMC
August 2020

Fluorinated scaffolds for antimalarial drug discovery.

Expert Opin Drug Discov 2020 06 21;15(6):705-718. Epub 2020 Mar 21.

Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi , Delhi, India.

Introduction: The unique physicochemical properties and chemical diversity of organofluorine compounds have remarkably contributed for their wide utility in the area of pharmaceuticals, materials and agrochemicals. The noteworthy characteristics of fluorine include high electron affinity, lipophilicity and bioavailability, extending the half-life of the drugs. The incorporation of fluorine substituents, particularly trifluoromethyl groups, into organic molecules has led to their high potency against various diseases, including malaria. Hence, organofluorinated molecules offer valuable avenues for the design of new drug candidates against malaria.

Areas Covered: In this review, the authors discuss the importance of fluorine substituents present in the chemical compounds, and their potential applications for antimalarial drug discovery.

Expert Opinion: Fluorinated molecules represent a reliable strategy to develop new antimalarial drugs. Fluorine or fluorinated groups have been identified as a promising precursor, and their presence in approximately twenty-five percent of approved drugs is notable. Selective fluorination of chemical entities has the potential to be applied not only to improve the activity profile against the malaria parasite, but could be extrapolated for favorable pharmacological applications. Hazardous reagents such as HF, F and SF used for fluorination, are not considered as safe, and therefore, this process remains challenging, particularly for the pharmaceutical industry.
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http://dx.doi.org/10.1080/17460441.2020.1740203DOI Listing
June 2020

Small Molecules Effective Against Liver and Blood Stage Malarial Infection.

Curr Top Med Chem 2019 ;18(23):2008-2021

Department of Chemistry, Miranda House, University of Delhi, Delhi-110007, India.

Malaria is a lethal disease causing devastating global impact by killing more than 8,00,000 individuals yearly. A noticeable decline in malaria related deaths can be attributed to the most reliable treatment, ACTs against P. falciparum. However, the cumulative resistance of the malaria parasite against ACTs is a global threat to control the disease and, therefore the new effective therapeutics are urgently needed, including new treatment approaches. Majority of the antimalarial drugs target BS malarial infection. Currently, scientists are eager to explore the drugs with potency against not only BS but other life stages such as sexual and asexual stages of the malaria parasite. Liver Stage is considered as one of the important drug targets as it always leads to BS and the infection can be cured at this stage before it enters into the Blood Stage. However, a limited number of compounds are reported effective against LS malaria infection probably due to scarcity of in vitro LS culture methods and clinical possibilities. This mini review covers a range of chemical compounds showing efficacy against BS and LS of the malaria parasite's life cycle collectively (i.e. dual stage activity). These scaffolds targeting dual stages are essential for the eradication of malaria and to evade resistance.
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http://dx.doi.org/10.2174/1568026619666181129143623DOI Listing
January 2019