DESIGN, SYNTHESIS AND EVALUATION OF NITRIC OXIDE-RELEASING DERIVATIVES OF N-(n-BUTYL)MATRINIC ACID AND N-(n-BUTYL)MATRINOL AS ANTI-HEPATOCELLULAR CARCINOMA AGENTS

A series of novel furoxan-based derivatives of N-n-butyl matrinic acid (9 a-m) and N-n-butyl matrinol (10a-m) were synthesized and their anti-human hepatocellular carcinoma (HCC) activities were evaluated. All derivatives displayed potential inhibition of HepG2 cell proliferation. Among these derivatives, compounds 9a-f, 9j and 10b, 10g-i (IC50: 0.69-4.66 mu M) were superior to 5-FU (IC50: 5.82 mu M). The further study showed that compounds 9a, 9c and 9f had higher antiproliferative activity on human hepatocellular carcinoma cells Bel-7402 (IC50: 2.55-3.26 mu M) and SMMC-7721 (IC50: 5.26-5.79 mu M).