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

doi:10.3390/molecules23061494

Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species

Molecules. 2018 Jun 20;23(6):1494. doi: 10.3390/molecules23061494.

Authors

Laila S Espindola^{1

2}, Renata G Dusi^{3

4}, Daniel P Demarque⁵, Raimundo Braz-Filho⁶, Pengcheng Yan^{7

8}, Heidi R Bokesch^{9

10}, Kirk R Gustafson¹¹, John A Beutler¹²

Affiliations

¹ Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil. darvenne@unb.br.
² Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. darvenne@unb.br.
³ Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil. renatadusi@hotmail.com.
⁴ Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. renatadusi@hotmail.com.
⁵ Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil. dpdemarque@gmail.com.
⁶ 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. braz@uenf.br.
⁷ Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. yanpc@wzmc.edu.cn.
⁸ School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. yanpc@wzmc.edu.cn.
⁹ Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. bokeschh@mail.nih.gov.
¹⁰ Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21702, USA. bokeschh@mail.nih.gov.
¹¹ Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. gustafki@mail.nih.gov.
¹² Molecular Targets Program, National Cancer Institute, Frederick, MD 21702, USA. beutlerj@mail.nih.gov.

Abstract

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.

Keywords: Brazilian Cerrado biome; Celastraceae; Cheiloclinium cognatum; NCI-60 cancer cell line; Plenckia populnea; Salacia crassifolia; Salacia elliptica; cytotoxic activity; pristimerin.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / metabolism
Antineoplastic Agents / therapeutic use
Celastraceae / metabolism*
Cell Line, Tumor
Cell Survival / drug effects
Drug Screening Assays, Antitumor
Humans
Metabolomics / methods*
Pentacyclic Triterpenes
Plant Extracts / chemistry*
Plant Roots / chemistry
Salacia / chemistry*
Structure-Activity Relationship
Triterpenes / chemistry*
Triterpenes / isolation & purification
Triterpenes / metabolism
Triterpenes / therapeutic use

Substances

Antineoplastic Agents
Pentacyclic Triterpenes
Plant Extracts
Triterpenes
celastrol