Design, synthesis and anti-proliferative effects in tumor cells of new combretastatin A-4 analogs

A total of 11 novel combretastatin A-4 (CA-4) analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes: (i) hydrogenated derivatives, (ii) ethoxyl derivatives, (iii) amino derivatives and (iv) pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure–activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study.

Graphical abstractA total of 11 novel CA-4 analogs were designed, synthesized and evaluated for the anti-proliferative effects in tumor cells. The biological potency was affected by multiple structural features.Figure optionsDownload full-size imageDownload as PowerPoint slide