Dihydro-β-agarofuran sesquiterpenes isolated from Celastrus vulcanicola as potential anti-Mycobacterium tuberculosis multidrug-resistant agents

In the present study, we report four new dihydro-beta-agarofuran sesquiterpenes (1-4), which were isolated from the leaves of Celastrus vulcanicola, in addition to five derivatives (5-9). Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, X-ray studies, chemical correlations and biogenetic means. Compounds 1-9 and the previously reported sesquiterpenes 10-25 have been tested as potential antimycobacterial agents against sensitive and resistant Mycobacterium tuberculosis strains. 1 alpha-Acetoxy-6 beta,9 beta-dibenzoyloxy-dihydro-beta-agarofuran (20) exhibited antituberculosis activity against the MDR TB strain with a MIC value of 6.2 mu g/mL, comparable to or better than isoniazid or rifampin, two of the best first-line drugs commonly used in the treatment of TB. The structure-activity relationship is discussed. (C) 2011 Elsevier Ltd. All rights reserved.