Abstract
Oleanolic acid (1), ursolic acid (2), hederagenin (3), betulinol (4), betulinic acid (5), and glycyrrhetinic acid (6) are obtained from acorn/licorice industrial wastes with common triterpenoid structure as a model set for esterification. Eight 3,4,5-methoxybenzoyl triterpenoid derivatives (1a–6a), including four new derivatives (1a, 3a–1, 3a–2, and 3a–3), are synthesized by classical procedures. Their antitumor and anti-hepatic fibrosis activities are evaluated on four human tumor cell lines and t-HSC/Cl-6 cells. Derivative 1a shows maximum antiproliferative effects against all cell lines, especially against tumor cells with IC50 values in the range of 5.32–15.23 μM, but does not affect the viability of normal cells. The anti-tumor mechanisms of 1a are also investigated by western blot and docking studies. The 3,4,5-methoxybenzoyl triterpenoids offers an intriguing solution for naturally derived antitumor drugs and may be invaluable for further development of cancer therapy.
Graphical Abstract
Disclosure statement
The authors declare no conflict of interest.
Funding
The research was supported by National Nature Science Foundation of China (Grant No. 81703389), Education fund item of Liaoning Province (201610163L35), Youth development support plan of Shenyang Pharmaceutical University (ZQN2016023), E&T modern center for Natural Products of Liaoning Province of China (No. 2008402021), Construction of R&D institute of state original new drugs at Benxi of Liaoning Province (2009ZX09301-012-105B).