The Sapotaceae as a source of antitubercular metabolites and isolation of antimycobacterial pentacyclic triterpenes from Sideroxylon inerme

Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, infects approximately one-third of the world's population. Other Mycobacterium species including the zoonotic M. bovis and nontuberculous mycobacteria such as M. kansasii and M. fortuitum also infect humans, especially those with compromised immunity. Preliminary investigations showing good in vitro antimycobacterial activity in plants of the Sapotaceae family encouraged further study for novel antitubercular chemicals. Ten Sapotaceae species were tested for antimycobacterial efficacy against a panel of non-pathogenic mycobacteria as well as M. bovis and M. tuberculosis strains. The extracts were screened for cytotoxicity against Vero kidney and C3A human liver cells. From a bulk extraction of Sideroxylon inerme leaves, active compounds were isolated using bioassay-guided fractionation. The extract was tested for mutagenicity in the Ames and comet assays.

All Sapotaceae extracts had some antimycobacterial activity, with highest activity against M. smegmatis. M. fortuitum was relatively resistant while M. aurum and M. bovis BCG were moderately susceptible. Activity against the infectious M. bovis and M. tuberculosis aligned best with results against M. bovis BCG, supporting the use of this species as a non-pathogenic, fast-growing model organism for investigating antitubercular activity of plant extracts. Two pentacyclic triterpenes, alpha-amyrin and 3-beta-hydroxyolean-12-en-27-oic acid, isolated from Sideroxylon inerme had good activity against M. smegmatis and low cytotoxicity. The extract of this species showed no mutagenicity in the Ames test and relatively little genotoxicity in the comet assay. This appears to be the first time that these compounds have been reported from S. inerme.