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

Synthesis of novel SN38-aspirin pro drugs for the treatment of hepato cellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause ofcancer-related death worldwide. However, there is no effective chemotherapeutic treatment for HCC and its prognosisremains poor. Consequently, it is urgent to find an efficient antitumor agent to treat HCC. In this study, 7-ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100–1000times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs. Their structures were characterized by1 H NMR and elemental analysis. The in vitro anticancer activities of these compounds on two human hepatocellularcarcinoma cell lines (BEL-7404 and HepG2) and preliminary mechanisms of action were explored. Our data indicatedthat these compounds decreased the viability of cancer cell lines in a concentration- and time-dependent manner. Amongthem, compound 4b significantly inhibited cell viability of HepG2 cells (IC 50 = 0.1208 µ M) when compared with CPT-11 (IC 50 = 18.4267 µ M). Furthermore, compound 4b blocked HepG2 cell migration and invasion in vitro. These findingssuggest that compound 4b may be used as a promising anticancer agent against HCC.

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