Synthesis and biological evaluation of asiatic acid derivatives as c-Kit inhibitors.

Totally fifteen inhibitors of c-Kit based on asiatic acid (AA) derivatives were designed and synthesized with modification at C-2, C-3, C-23 and C-28 of AA. Their structures were confirmed by HRMS,1H NMR and 13C NMR. In vitro activity assay showed that these compounds can inhibit the proliferation of A549, SGC-7901 and MCF-7 cells, and especially compound II2 showed better inhibitory activity on these tumor cells, similar to the positive control drug Sorafenib. Mechanistically, selected compound may inhibit the proliferation of A549 cells by inhibiting c-Kit protein expression, which may be a promising lead compound for cancer therapy.