Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species
Laila S. Espindola,
Renata G. Dusi,
Daniel P. Demarque,
Raimundo Braz-Filho,
Pengcheng Yan,
Heidi R. Bokesch,
Kirk R. Gustafson,
John A. Beutler
Affiliations
Laila S. Espindola
Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil
Renata G. Dusi
Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil
Daniel P. Demarque
Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil
Raimundo Braz-Filho
FAPERJ/Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ and Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil
Pengcheng Yan
Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA
Heidi R. Bokesch
Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA
Kirk R. Gustafson
Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA
John A. Beutler
Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA
The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI50 of 0.17 μM, while compound 1 had a mean GI50 of 8.7 μM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI50 of 0.3 μg·mL−1). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia.
