Design, Synthesis, and Investigation of Cytotoxic Activity of cis-Vinylamide-Linked Combretastatin Analogues as Potential Anticancer Agents

The combretastatins (cis-stilbenoid molecules) have received significant interest because of their simple chemical structures, excellent antiproliferative activity, and novel anti-tubulin molecular mechanism action. Significant efforts been carried out aiming at stabilizing the active cis-isomers. A new series cis-vinylamide derivatives containing trimethoxyphenyl moiety were synthesized characterized. Their anticancer activities evaluated in vitro against MCF-7 breast cancer cell line. Compounds 2f, 3, 5 displayed potent cytotoxic activity line compared with CA-4 as reference compound. microtubule polymerization assay flow cytometry analysis confirmed that compound 3 was related to inhibitory tubulin polymerization. Compound showed pro-apoptotic by inducting a increase percentage pre-G1 phase DNA untreated control. inferred fluorescent annexin V/PI positive apoptotic cells. It also increased level caspase