IMR Press / FBL / Volume 13 / Issue 10 / DOI: 10.2741/2974

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
4-Thiazolidinones: a novel class of hepatitis C virus NS5B polymerase inhibitors
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1 Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103
2 Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439
3 Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Haydarpasa, 34668 Istanbul, Turkey

*Author to whom correspondence should be addressed.

Academic Editor: Deborah Taylor

Front. Biosci. (Landmark Ed) 2008, 13(10), 3857–3868;
Published: 1 May 2008
(This article belongs to the Special Issue Innate immunity and protein synthesis)

In a quest to identify novel compounds targeting HCV viral replicase, we evaluated a new series of 4-thiazolidinone derivatives (18 compounds). Our in vitro NS5B RdRp inhibition analysis with a series of 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl / substituted phenyl)-4-thiazolidinone-3-yl] amides (1-7) yielded IC50 values ranging between 45-75 microM. Of these, lead compound 6: 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid[2-(2-fluorophenyl)-4-thiazolidinone-3-yl]amide exhibited an IC50 value of 48 microM and inhibited NS5B non-competitively with respect to UTP and exhibited a mixed mode of inhibition with respect to RNA. Molecular docking of thiazolidinone derivatives within the allosteric site of NS5B yielded significant correlation between their calculated binding affinity and IC50 values. Taken together, these data suggest that the 4-thiazolidinone scaffold may be optimized for generating new analogues with improved anti-NS5B potency.

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