Synthesis of Diaryl Pyrrolones Derivatives as Combretastatin A-4

Combretastatins-A4 (CA-4) is a natural product with anticancer activity. However, only the cis-isomer exhibits strong antitubulin activity, but the cis-isomer tends to isomerize to the inactive trans-isomer. Thus, this paper reports that an additional pyrrolidone ring was used to replace the cis double bond to arrest the cis-conformation, and a series of 3,4-diaryl pyrrolediones and 3,4-diaryl pyrrolones as CA-4 analogues were synthesized via a four steps reaction from 3,4-dimethoxyacetophenone and 3-fluoro-4-methoxy acetophenone. The structure of the new compounds was confirmed by 1H NMR, 13C NMR, ESI-MS and elemental analysis. The in vitro activities of CA-4 analogues against HL-60, SMMC-7721 and A549 human cancer cell lines were tested using colorimetric MTT assay and the results indicate that they show significant antitumor activity.