Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives

Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluatedin vitrousing different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluatedin vivousing a larval zebrafish model. Among the derivatives, compounds4–10showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds11–17had significantly less effects. The new derivative10was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative10had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.Keywords:asiatic acid;amino acid derivatives;anti-tumor activity;anti-angiogenic effect;stability;HPLC analysis