Synthesis, anticancer evaluation, and molecular docking study of some arylidenehydrazono analogues

A series of 2-(arylidenehydrazono)-5-(2-oxo-2-arylethyl)thiazolidin-4-one derivatives was synthesized, characterized by spec-tral analyses and evaluated for their in vitro antitumor activity. The IC50 determination of compounds was investigated on the human breast cancer cell line MCF-7. Among the series, compounds 3, 6, 10, 16, 17, and 24 showed remarkable anticancer activity with mean IC50 values 2.34, 0.73, 2.69, 3.40, 1.18, and 1.76 mu g/mL, respectively, against MCF-7 cancer cells. Compound 16 enhanced the concentration of caspase-9, inhibited the concentration of Ki67 and showed a profound reduction in the amount of MMP9 secreted into the medium of MCF-7-treated cells. Furthermore, compound 16 revealed anti-angiogenic ac-tivity through downregulation of the concentration of VEGF in the medium of MCF-7-treated cells. Compound 16 exerted cytotoxic effects on MCF-7 tumor cells via antiproliferative, apoptotic, anti-angiogenic, and antimetastatic activities. Molecu-lar docking methodology was performed for the most effective anticancer compounds to rationalize the possible interactions with active site of VEGFR-2 enzyme.