We herein report the anti-cancer activities of some synthesized pyridine derivatives substituted with thiazole, pyrazole and triazole moieties. A series of these derivatives 1-12 were synthesized and evaluated as anti-inflammatory, analgesic, anticonvulsant and antiparkinsonian agents before. Twelve compounds were conveniently screened for their in vitro cytoyoxicity against a wide rannge of cell lines and they are also showed potent activities against renal and prostate cancer cell lines. The in vivo antirenal cancer and antiprostate cancer of the most active in vitro compounds was estimated and founded highly potent. In search for the mechanism of action of anticancer activities it was foundeded that these compounds exert its action via histone decarboylase inhibition and inhibition of p53 ubiquitination.