Etodolac Thiosemicarbazides: A novel class of hepatitis C virus NS5B polymerase inhibitors

Year 2013, Volume: 17 Issue: 2, 138 - 146, 07.03.2014

Pelin Çıkla Payal Arora Amartya Basu Tanaji Talele Neerja Kaushik-basu Şükriye Küçükgüzel

Abstract

ABSTRACT: A novel series of new etodolac hydrazide derivatives, 1-[2-(1,8-diethyl-1,3,4,9-
tetrahydropyrano[3,4-b]indole-1-yl)acetyl]-4-alkyl/aryl thiosemicarbazides [3a-h] have been
synthesized in this study. The structures of the new compounds were determined by spectral
(FT-IR, 1H-NMR, 13C-NMR and LC-MS) methods. Inhibition of hepatitis C virus NS5B RNA
dependent RNA polymerase activity by etodolac thiosemicarbazides was evaluated in vitro
by primer dependent elongation assays. The most active compounds of this series were
3a (SGK 224), 3d (SGK 227) and 3e (SGK 229) with IC50 values of 18.7 μM, 29.2 μM and 16.8
μM, respectively. Binding mode investigations of the most active compound 1-[2-(1,8-diethyl-
1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetyl]-4-allyl thiosemicarbazide (3e) suggested
that TP-II of HCV NS5B polymerase may be the potential binding site for etodolac thiosemicarbazides
and provided clues for modifications to improve the potency of etodolac derivatives.
KEYWORDS: thiosemicarbazide, etodolac, Hepatit C NS5B polymerase, pyrano[3,4-b]indole.

Keywords

thiosemicarbazide, etodolac, Hepatit C NS5B polymerase, pyrano[3, 4-b]indole.

Etodolac Thiosemicarbazides: A novel class of hepatitis C virus NS5B polymerase inhibitors

Abstract

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