Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 2013 , Vol 17 , Issue 2
Etodolac Thiosemicarbazides: A novel class of hepatitis C virus NS5B polymerase inhibitors
Pelin Çıkla1, Payal Arora2, Amartya Basu2, Tanaji T. Talele3, Neerja Kaushik-Basu2, Ş.Güniz Küçükgüzel1
1Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Turkey
2UMDNJ-New Jersey Medical School, Department of Biochemistry and Molecular Biology, New Jersey, USA
3St. John’s University College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences, New York, USA
DOI : 10.12991/201317382 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.
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