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

Cikla-Suzgun P. , Kaushik-Basu N., Basu A., Arora P., Talele T. T. , Durmaz I., ...More

Journal of Enzyme Inhibition and Medicinal Chemistry, vol.30, no.5, pp.778-785, 2015 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 5
  • Publication Date: 2015
  • Doi Number: 10.3109/14756366.2014.971780
  • Title of Journal : Journal of Enzyme Inhibition and Medicinal Chemistry
  • Page Numbers: pp.778-785
  • Keywords: 1,2,4-Triazole-3-thione, etodolac, HCV NS5B polymerase, hepatocellular carcinoma, HUMAN HEPATOCELLULAR-CARCINOMA, DERIVATIVES, CYCLOOXYGENASE-2, CYTOTOXICITY, INHIBITION, DISCOVERY, HYDRAZIDE


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 mu 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 mu M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound.