Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues.

Bioorganic & medicinal chemistry letters

PubMedID: 25529737

Guan Q, Zuo D, Jiang N, Qi H, Zhai Y, Bai Z, Feng D, Yang L, Jiang M, Bao K, Li C, Wu Y, Zhang W. Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues. Bioorg Med Chem Lett. 2014;.
A series of new CA-4 analogues bearing maleic anhydride/N-substituted maleimide moiety were synthesized via a microwave-assisted process. They were evaluated for the anti-proliferative activities against three tumor cell lines (SGC-7901, HT-1080 and KB). Most compounds showed moderate potencies in micromolar range, with the most promising analogue 6f showing active at submicromolar concentration against HT-1080 cancer cells which was selected to investigate the antitumor mechanisms. In addition, molecular docking studies within the colchicine binding site of tubulin were also in good agreement with the tubulin polymerization inhibitory data and provided a basis for further structure-guided design of novel CA-4 analogues.