Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles

Date
2015
Authors
Çikla-Süzgün P.
Kaushik-Basu, N.
Basu, A.
Arora P.
Talele, T.T.
Durmaz I.
Çetin-Atalay, R.
Küçükgüzel, S.G.
Advisor
Instructor
Source Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Print ISSN
14756366
Electronic ISSN
Publisher
Taylor and Francis Ltd
Volume
30
Issue
5
Pages
778 - 785
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Abstract

Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.

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Other identifiers
Book Title
Keywords
1,2,4-Triazole-3-thione, etodolac, HCV NS5B polymerase, hepatocellular carcinoma, 5 [(1,8 diethyl 1,3,4,9 tetrahydropyrano[3,4 b]indole 1 yl) methyl] 4 benzyl 2,4 dihydro 3h 1,2,4 triazole 3 thione, 5 [(1,8 diethyl 1,3,4,9 tetrahydropyrano[3,4 b]indole 1 yl) methyl] 4 methyl 2,4 dihydro 3h 1,2,4 triazole 3 thione, antivirus agent, cyclooxygenase 1, cyclooxygenase 2, etodolac, nonstructural protein 5B, triazole derivative, unclassified drug, antineoplastic activity, antiviral activity, Article, drug synthesis, growth inhibition, Hepatitis C virus, hepatocellular carcinoma cell line, human, human cell, IC50, liver cancer cell line, priority journal, virus infection
Citation
Published Version (Please cite this version)