IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Lupane triterpenoids with inhibitory activity against prostate cancer cells
Autor/es:
MARÍA JULIA CASTRO; VALERIA P. CAREAGA; PAULA SACCA; JUAN C. CALVO; MARTA S. MAIER; MARÍA B. FARAONI; ANA P. MURRAY
Lugar:
Olomouc
Reunión:
Congreso; Trends in Natural Products Research; 2014
Resumen:
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, PC-3 (androgen independent) and LNCaP
(androgen dependent). Compounds 2, 4, 6 and 7 exhibited moderate inhibitory activities against the prostate
cancer cells PC3 with IC50 values in the range 58-73μM. Compounds 2 and 4 also showed moderated 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.