Synthesis and Antitumor Evaluation in Vitro of NO-Donating Ursolic Acid-Benzylidene Derivatives

Antitumor activity of triterpenoid and its derivatives has attracted great attention recently. Our previous efforts led to the discovery of a series of NO-donor betulin derivatives with potent antitumor activity. Herein, we prepared eight compounds derived from ursolic acid (UA). All the compounds were evaluated for their in vitro cytotoxicity against four human cancer cell lines (HepG-2, MCF-7, HT-29 and A549). Among the compounds tested, compound 4a was found to be most active against HT-29 (IC50=4.28 mu m). Further biological assays demonstrated that compound 4a could induce cell cycle arrest at G1 phase and apoptosis in a dose-dependent manner. In addition, compound 4a was found to upregulate pro-apoptotic Bax, p53 and downregulate anti-apoptotic Bcl-2. All these results suggested that compound 4a is a potential candidate drug for the therapy of colon cancer.