Antimycobacterial activity of sesquiterpenes isolated from Celastrus vulcanicola (Celastraceae)

Species of the family Celastraceae are widespread in tropical and subtropical regions of the world, including Central and South America. Over the last 30 years, a large variety of biologically active metabolites have been identified from members of this family, including maytansinoids, quinone-methide triterpenes, and sesquiterpenoids based on the 5,11-epoxy-5β-10α-eudesman-4-(14)-ene skeleton. These compounds possess a broad spectrum of biological activities, such as anti-HIV, reversing multidrug resistance (MDR) and chemopreventive activities [1].

Tuberculosis (TB) continues to be a major health concern, and its recent rise is associated with the emergence of the human immunodeficiency virus (HIV) and the rapid spread of multidrug-resistant (MDR-TB) strains. There is now recognition that new drugs to treat TB are urgently required, specifically for use in shorter treatment regimens and which can be employed to treat MDR and latent diseases [2].

In the course of our research for bioactive compounds from Celastraceae species, herein we report the isolation of twenty five dihydro-β-agarofuran sesquiterpenoids isolated from Celastrus vulcanicola. Their structures were determined by spectroscopic methods, including 1D and 2D NMR experiments.

The compounds were tested for anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv and isoniazide and rifampicine resistant (MDR-TB) strains. Seven of the compounds exhibited activity against the MDR-TB strain, with values of minimal inhibitory concentration (MIC) ranging from 6.2 to12.5µg/mL.

Acknowledgements: We are indebted to the DGES (CTQ2006–13376/BQU) and FICIC (01/2007) projects for financial support. Torres DF. and Osorio AA. Thanks to the Agencia Española de Cooperación Internacional (MAE-AECI) for a fellowship.

References: 1. Gao, J. M. et al. (2007) Nat. Prod. Rep. 24: 1153–1189.

2. Shah, N. S. et al. (2007) Emerg. Infect. Dis. 13: 380–387.