Design and Synthesis of Novel 3β-O-Succinyl-lupeol and 3β-O-Maleicyl-lupeol Derivatives as Potential Antitumor Agents

Abstract

Lupeol is a natural pentacyclic triterpenoid with a wide range of biological activities. To enhance the antitumor efficacy of lupeol, eight lupeol-3-succinate derivatives and seven lupeol-3-maleate derivatives were designed and synthesized. The new compounds were evaluated for their cytotoxic activities against human lung cancer A549 cell line, human liver cancer HepG2 cell line, and human breast cancer MCF-7 cell line. All compounds were found to show better cytotoxic activity in vitro than lupeol. Among them, lup-20(29)-en-3β-yl 4-oxo-4-(pyrrolidin-1-yl)butanoate displayed remarkable cytotoxic activity against lung cancer A549 cells, with an IC₅₀ of 2.33 μM, and potently induced apoptosis in lung cancer A549 cells. The mechanism of action of lup-20(29)-en-3β-yl 4-oxo-4-(pyrrolidin-1-yl)butanoate can be subjected to further evaluation. It has potential to become a novel anti-tumor agent through further structural modification.