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-β-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. 1α-Acetoxy-6β,9β-dibenzoyloxy-dihydro-β-agarofuran (20) exhibited antituberculosis activity against the MDR TB strain with a MIC value of 6.2 μg/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.

A series of natural and derivative dihydro-β-agarofuran sesquiterpenes have been tested against sensitive and resistant Mycobacterium tuberculosis strains. Among those tested, 20 exhibited promising anti-MDR TB activity. Their stereostructures were elucidated by NMR and X-ray analysis.Figure optionsDownload as PowerPoint slide