Synthesis and anti-hepatocellular carcinoma activity of aminopyridinol-sorafenib hybrids.

Sorafenib is recommended as the primary therapeutic drug for patients with hepatocellular carcinoma. To discover a new compound that avoids low response rates and toxic side effects that occur in sorafenib therapy, we designed and synthesized new hybrid compounds of sorafenib and 2,4,5-trimethylpyridin-3-ols. Compound was selected as the best of 24 hybrids that inhibit each of the four Raf kinases. The anti-proliferative activity of in HepG2, Hep3B, and Huh7 cell lines was slightly lower than that of sorafenib. However, in H6c7 and CCD841 normal epithelial cell lines, the cytotoxicity of was much lower than that of sorafenib. In addition, similar to sorafenib, compound inhibited spheroid forming ability of Hep3B cells and tumour growth in a xenograft tumour model of the chick chorioallantoic membrane implanted with Huh7 cells. Compound may be a promising candidate targeting hepatocellular carcinoma with low toxic side effects on normal cells.