Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-α-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 μg/mL against both strains. The methylated derivatives 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13), mulin-11,13-dien-20-oic acid methyl ester (15) and mulinenic acid methyl ester (23) proved to be more active than the parent compounds.GMMS wishes to thank Consejo Nacional de Ciencia y Tecnología-México for a postdoctoral fellowship, and Programa de Cooperación Internacional de la Coordinación de Investigación en Salud-IMSS, for supporting a research stay at Universidad de Antofagasta, Antofagasta, Chile. LAL wishes to acknowledge FONDECYT-Chile support for this project (Grant No. 1060339). The evaluation of antituberculosis activity in this collaborative work was supported by Instituto Mexicano del Seguro Social (Project 2008-1908-4). Research was performed under the auspices of the EULADIV Alfa Project and FOMIX-Yucatán Project No. 66262