A Thiazole Analogue Exhibits an Anti-Proliferative Effect in Different Human Carcinoma Cell Lines and Its Mechanism Based on Molecular Modeling

Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.