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.