Synthesis of novel SN38-aspirin prodrugs for the treatment of hepatocellular carcinoma

Authors : Zhimin CHEN, Yi LUO, Aiping FANG, Chen FAN, Chenjuan ZENG

Pages : 929-939

View : 16 | Download : 7

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :Hepatocellular carcinoma insert ignore into journalissuearticles values(HCC); is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. However, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Consequently, it is urgent to find an efficient antitumor agent to treat HCC. In this study, 7-ethyl-10-hydroxycamptothecin insert ignore into journalissuearticles values(SN38);, the bioactive metabolite of the anticancer drug irinotecan insert ignore into journalissuearticles values(CPT-11);, which is 100-1000 times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs. Their structures were characterized by $^{1}$H~NMR and elemental analysis. The in vitro anticancer activities of these compounds on two human hepatocellular carcinoma cell lines insert ignore into journalissuearticles values(BEL-7404 and HepG2); and preliminary mechanisms of action were explored. Our data indicated that these compounds decreased the viability of cancer cell lines in a concentration- and time-dependent manner. Among them, compound 4b significantly inhibited cell viability of HepG2 cells insert ignore into journalissuearticles values(IC$_{50\, }$= 0.1208 $\mu $M); when compared with CPT-11 insert ignore into journalissuearticles values(IC$_{50}$ = 18.4267 $\mu $M);. Furthermore, compound 4b blocked HepG2 cell migration and invasion in vitro. These findings suggest that compound 4b may be used as a promising anticancer agent against HCC.
Keywords : 7 Ethyl 10 hydroxycamptothecin, aspirin, prodrug, hepatocellular carcinoma