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

摘要

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 evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds >4–>10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds >11–>17 had significantly less effects. The new derivative >10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative >10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.