Çıkla, Pelin Marmara University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry, Turkey , Arora, Payal University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Basu, Amartya University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Talele, Tanaji T. St. John’s University - College of Pharmacy and Health Sciences - Department of Pharmaceutical Sciences, USA , Kaushik-Basu, Neerja University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Küçükgüzel, Ş.Güniz Marmara University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry, Turkey

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

18760

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.

138

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

Journal of Research in Pharmacy

146