Çıkla-Süzgün Pelin, Kaushik-Basu Neerja, Basu Amartya, Arora Payal, Talele Tanaji T, Durmaz Irem, Çetin-Atalay Rengül, Küçükgüzel Ş Güniz
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Marmara University , İstanbul , Turkey .
J Enzyme Inhib Med Chem. 2015;30(5):778-85. doi: 10.3109/14756366.2014.971780.
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(50) value of 14.8 µM. 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(50) value of 4.29 µM. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound.
花生四烯酸是一种从细胞膜磷脂中释放出来的不饱和脂肪酸。非甾体抗炎药是花生四烯酸代谢中环氧化酶（COX - 1、COX - 2和COX - 3）的作用靶点。COX - 2在致癌过程中的这种机制会引发癌症。此外，COX - 2在肝癌发生的早期阶段起作用。丙型肝炎病毒（HCV）感染是肝硬化和肝细胞癌（HCC）的病因。我们研究的目的是开发针对HCV的有效药物。已经合成了一系列新型的依托度酸1,2,4 - 三唑衍生物（4a - h），并研究了它们对HCV NS5B聚合酶的活性。发现化合物4a活性最高，IC(50)值为14.8 μM。根据这些结果，对化合物4a在肝癌细胞系（Huh7、Mahlavu、HepG2、FOCUS）上进行了抗癌活性筛选。化合物4a对Huh7人肝癌细胞系显示出抗癌活性，IC(50)值为4.29 μM。因此，化合物4a可被视为一种新型的抗癌和抗HCV先导化合物。
