Cytotoxic and antivascular 1-methyl-4-(3-fluoro-4-methoxyphenyl)-5-(halophenyl)-imidazoles.

A series of 1-methyl-4,5-diphenylimidazoles 6 with various patterns of m-halogen substitution at the 5-phenyl ring were tested for cytotoxicity in cancer and nonmalignant cell lines and for their capacity to prevent tube formation in HUVEC cultures. Unlike the monofluoro and difluoro derivatives 6a and 6e, the monobromo and diiodo analogs 6c and 6h were strongly cytotoxic and inhibited the polymerization of tubulin and the tube formation by HUVEC. The dibromo derivative 6g displayed a unique selectivity for KB-3-1 cervix and PC-3 prostate cancer cells. It also inhibited the tube formation by HUVEC and the polymerization of tubulin which is indicative of its potential antiangiogenic activity in solid tumors.