Chiral gossypol derivatives: evaluation of their anticancer activity and molecular modeling

To better use gossypol to find promising anticancer compounds, a series of new and known bis-Schiff base analogs of chiral gossypol were synthesized, and their anticancer activity on HeLa, U87 and M85 cells was tested. The results showed that through a simple chemical modification, less active (+)-gossypol could be converted into more active derivatives. When compared with (-)-gossypol, many more potent compounds that could be the promising anticancer agents were found, and some of them were more potent than the anticancer drug Cisplatin against all three cancer cell lines. By eliminating target functional groups, we observed that the major contributor to the anticancer activity of chiral gossypol seemed to be the phenolic groups, and not the aldehyde groups. Through comprehensive analysis of chiral gossypol analogs, the structure-activity relationships were elaborated.