Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
Author
Çikla-Süzgün P.
Kaushik-Basu, N.
Basu, A.
Arora P.
Talele, T.T.
Durmaz I.
Çetin-Atalay, R.
Küçükgüzel, S.G.
Date
2015Source Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Print ISSN
14756366
Publisher
Taylor and Francis Ltd
Volume
30
Issue
5
Pages
778 - 785
Language
English
Type
ArticleItem Usage Stats
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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 IC<inf>50</inf> 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 IC<inf>50</inf> 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.
Keywords
1,2,4-Triazole-3-thioneetodolac
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