Abstract
A new lupane caffeoyl ester, lup-20(29)-ene 3 beta-caffeate-30-al (7), and a new oleanane-type triterpene, 3 beta-hydroxyolean-13(18)-en-12-one (17), were isolated from the aerial parts of Dobera glabra (Forssk), along with ten known triterpenes, including seven lupane-type lupeol (1), 30-nor-lup-3 beta-ol-20-one (2), increment (1)-lupenone (3), lup-20(29)-en-3 beta,30-diol (4), lupeol caffeate (5), 30-hydroxy lup-20(29)-ene 3 beta-caffeate (6), and betunaldehyde (8); three oleanane-type compounds were also identified, comprising delta-amyrone (15), delta-amyrin (16), and 11-oxo-beta-amyrin (18); together with six sterols, comprising beta-sitosterol (9), stigmasterol (10), 7 alpha-hydroxy-beta-sitosterol (11), 7 alpha-hydroxy-stigmasterol (12), 7-keto-beta-sitosterol (13), and 7-keto-stigmasterol (14). Their structures were elucidated using a variety of spectroscopic techniques, including 1D (H-1, C-13, and DEPT-135 C-13) and 2D (H-1-H-1 COSY, H-1-C-13 HSQC, and H-1-C-13 HMBC) nuclear magnetic resonance (NMR) and accurate mass spectroscopy. Subsequently, the different plant extracts and some of the isolated compounds (1-9, 11 and 13) were investigated for their possible cytotoxic activity in comparison to cisplatin against a wide array of aggressive cancer cell lines, such as colorectal cancer (HCT-116), hepatocellular carcinoma (HepG-2), and prostate cancer (PC-3) cell lines. Compound 11 displayed broad cytotoxicity against all of the tested cell lines (IC50 approximately equal to 8 mu g/mL in all cases), and a high safety margin against normal Vero cells (IC50 = 70 mu g/mL), suggesting that 11 may be a highly selective and effective anticancer agent candidate. Notably, the evidence indicated that the mode of action of compound 11 could possibly consist of the inhibition of phosphodiesterase I (80.2% enzyme inhibition observed at 2 mu M compound concentration).