Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents

Antiviral Research
Cai LinJiancun Zhang

Abstract

Among many subtypes of influenza A viruses, influenza A(H1N1) and A(H3N2) subtypes are currently circulating among humans (WHO report 2014-15). Therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. To this regard, the design and synthesis of nucleoside analog inhibitors as potential anti-influenza A agents is a very active field of research nowadays. In this study, we designed and synthesized a series of hitherto unknown 6-methyl-7-substituted-7-deaza purine nucleoside analogs, and evaluated for their biological activities against influenza A virus strains, H1N1 and H3N2. From the viral inhibition assay, we identified some effective compounds, among which, compounds 5x (IC50 = 5.88 μM and 6.95 μM for H1N1 and H3N2, respectively) and 5z (IC50 = 3.95 μM and 3.61 μM for H1N1 and H3N2, respectively) demonstrated potent anti-influenza A activity. On the basis of selectivity index, we conceive that compound 5x may serve as a chemical probe of interest for further lead optimization studies with a general aim of dev...Continue Reading

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Citations

Oct 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·M Lourdes SciúE Laura Moyano
Sep 16, 2020·Molecular Diversity·Olga V AndreevaVladimir E Kataev
Feb 8, 2021·European Journal of Medicinal Chemistry·Xia LinWeisen Lan
Aug 11, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Cai LinSerge Van Calenbergh

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