Design, Synthesis and Anticancer Evaluation of Novel Series of Indibulin Analogues

摘要

Background: Cancer is an important cause of human death worldwide. During the lastdecades, many anticancer agents with anti-tubulin mechanism have been synthesized or extractedfrom nature and some of them also entered clinical use. Indibulin is one of the most potent tubulinpolymerization inhibitors with minimal peripheral neuropathy, which is a big problem by some ofthe antimitotic agents such as taxanes and vinka alkaloids. With respect to this giant benefit, hereinwe decided to design and synthesize novel indibulin related compounds and investigate theiranticancer activity against HT-29, Caco-2 and T47-D cancerous cell lines as well as NIH-T3T asnormal cell line.Objective: The aim of this study was to synthesize new anti-cancer agents and evaluates their cytotoxicactivity on diverse cancerous and normal cell lines.Methods: Target compounds were synthesized in multistep reaction and cytotoxic activity was investigatedby MTT cell viability assay.Results: Herein, nine novel target compounds were synthesized in moderate to good yield. Someof the compounds exerted good cytotoxic activity against cancerous cell lines. Annexin V/PI stainingshowed that compound 4g could induce apoptosis and necrosis in HT-29 cell line.Conclusion: It is valuable to do further investigation on compound 4g which showed the highestactivity against HT-29 and Caco-2 (IC50 values are 6.9 and 7 μM respectively). Also, synthesis ofnew derivatives of current synthesized compounds is suggested.