Synthesis And Bioevaluation Of Imide Derivates As Antitumor Agents

Objective: It was to exploit new imide antitumor angents, enchance naphthalimide and phthalimide antitumor activitives and reduce 5-Fluorouracil side effects. Methodes: Thirty-four compounds including twenty-one imide polyamine and thirteen imide 5-Fluorouracil conjugates, which are new compounds exept MINS (2-10c), were synthesized, bioevaluated and studied on 2-10f inducing B16 cell apoptosis. Results: (1) Naphthalimide polyamine conjugates were evaluated in vitro cytotoxicity, the results revealed seven compounds without substitued groups have more effctive than naphthalimide while the others with different ones have more effctive than Amonafide. Importantly, compound 2-10f can inhibit Top.II and induce B16 cell apoptosis via both the mitochondrial and membrane death receptor pathways. Their antitumor activity was effected by substituent groups, chains and tumor cells. They have also exhibited cell selectivity to cancer cells through the human hepatoma BEL-7402 and human normal hepatocyte QSG-7701 screens and intercalated DNA. (2) Phthalimide polyamine conjugates have little antitumor activity. (3) 5-Fu imide conjugates were less effective than 5-Fu in vitro and in vivo because of their structural speciality and chemical stablity, although some of them effectively inhibited the growth of tumor cells in vitro and liver cancer H22 in vivo. Conclusion: (1) Naphthalimide polyamine conjugates which are insteresting anticaner would lead for further study; (2) It can be deduced that the polyamine has selectivity to carry phthalimide with regard that phthalimide polyamine conjugates have little antitumor activity; (3) It was vital that free 5-fluorouracil be released from imide 5-Fluorouracil conjugates under physiological pH conditions as a result that they were less effective than 5-Fu in vivo.