Mechanistic elucidation and prediction of the anticancer activity of 1,3,4-thiadiazol-2-amide derivatives

Abstract

The development of the potent safer drugs is still urgently needed in the anticancer therapy. To better explore the structural requirements of 1,3,4-thiadiazol-2-amides for their focal adhesion kinase inhibitory activity and their antiproliferative activity towards MCF-7 and B16-F10 cells, six statistically significant and highly predictive quantitative structure-activity relationship models were established, and the corresponding design strategy was also proposed. Our results visualized the main steric and electrostatic profiles in their structures required for the anticancer activity, and showed that the effect of the size, number and the electronegative properties of the substituents in the aromatic rings on these anticancer activities was significant. Finally, the anticancer activity of a series of newly designed compounds was predicted and mutually validated by the established models, and some of which were better than that of the anticancer drug staurosporine.