Investigation of Cytotoxic Activity Properties of Etoxazole Towards Human Cancer and Healthy Cell Lines and Molecular Docking Studies.

Abstract

The effect of etoxazole on cancer cells was evaluated in vitro using different cell lines. In this context, its cytotoxic activity on breast (MCF-7), liver (HepG2), colon (DLD-1) and lung (A549) cancer cell lines was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method was used to determine the effects on cell viability. Tests were also performed on a healthy human embryonic kidney cell line (HEK-293T) to evaluate the selectivity of the compound. The results revealed that etoxazole showed varying degrees of antiproliferative activity in cancer cell lines. In particular, it showed the most potent inhibition effect with an IC₅₀ value of 33.18 µM in HepG2 cell line. In contrast, in the A549 cell line, the IC₅₀ value was measured as 91.38 µM, indicating that the compound had a lower cytotoxic effect in lung cancer cells. Etoxazole, which exhibited a more pronounced effect against liver cancer cells, showed moderate cytotoxicity in other cell lines. Moreover, the IC₅₀ value in healthy HEK-293T cells was found to be 1628.0 µM, which demonstrates that etoxazole has a high selectivity index and low toxicity towards normal cells. On the other hand, evaluations in the healthy HEK-293T cell line revealed that etoxazole has a selective effect. The IC₅₀ value in healthy cells was relatively high, suggesting that the compound may exhibit a specific cytotoxic activity against cancer cells. In general, etoxazole was found to have varying levels of cytotoxic activity in different cancer cell lines. The effect of the compound varied depending on the cell type and it was observed that it exhibited a more pronounced antiproliferative activity especially in liver cancer cells. These results indicate that etoxazole may be a promising candidate for hepatocellular carcinoma treatment. Furthermore, molecular docking simulations were conducted to evaluate the binding mode and affinity of the etoxazole ligand against the Kinase Insert Domain Receptor (PDB ID: 3WZE). The docking results indicated that etoxazole exhibited a binding energy of -8.6 kcal/mol and formed stable interactions within the active site, suggesting a high inhibitory potential. In particular, key stabilizing interactions were identified, including hydrogen bonds with ASP183 and a halogen bond with GLU72, further supporting the molecular affinity. These findings suggest that etoxazole may be the subject of further research as a potential anticancer agent.