Lupane triterpenoids with inhibitory activity against prostate cancer cells

CASTRO, MARÍA JULIA; CAREAGA, VALERIA P.; SACCA, PAULA; CALVO, JUAN C.; MAIER, MARTA SILVIA; FARAONI, MARÍA BELEN; ANA PAULA MURRAY

Olomouc

Congreso; Trends in Natural Products Research; 2014

Phytochemical Society of Europe, Palacký University Olomouc

Triterpenoids are naturally occurring compounds with ubiquitous distribution and a wide range of biological activities. Pentacyclic triterpenoids provide privileged structures for further modifications and structure activity relationship (SAR) studies. Lupanes in particular, have attracted attention since they exhibit a broad range of biological and pharmacological properties such as antitumor, anti-inflammatory, anti-HIV, anticholinesterase, insecticidal and antimalarial activities. Human prostate cancer (PCa) is the most common form of non-cutaneous cancer, and metastatic late-stage PCa represents a significant challenge with few successful treatment options. According to the most recent statistics available, prostate cancer is the most common cancer in American men, and second only to lung cancer in the number of cancer deaths. Every year, more than 200,000 men are diagnosed with prostate cancer, and more than 25,000 men die from it. In the present study, we aimed to determine the effect of natural and semisynthetic lupanes on PCa cells. Lupanes 1-3 have been isolated from Chuquiraga erinacea subsp. erinacea (Asteraceae), an endemic species growing wildly in our region (Fig. 1). Semisynthetic lupanes 4-12 have been prepared from calenduladiol (1) and lupeol (2) by transformations on the hydroxyl groups at C-3 and/or C-16, and also on the isopropenyl moiety. Compounds 1-12 were tested for their in vitro antitumor activity against two human prostate carcinoma cell lines, LNCaP (androgen dependent) and PC-3 (androgen independent). Compounds 2, 4, 6 and 7 exhibited moderate inhibitory activities against PC3 with IC50 values in the range 58-73 μM. Compounds 2 and 4 also showed moderate cell proliferative inhibitory effects on LNCaP cells with IC50 values of 46.05 ± 1.14 and 45.79 ± 1.06 μM, respectively. Compound 3, heliantrol B2, showed more potent activities with IC50 values of 56.10 ± 1.10 and 20.0 μM, for PC3 and LNCaP cells, respectively.