The Abyssomicin C family as in vitro inhibitors of Mycobacterium tuberculosis

The antimycobacterial efficacy of the abyssomicin C family of natural products, in addition to a key synthetic intermediate, has been investigated given their reported inhibition of Bacillus subtilis p-aminobenzoate biosynthesis. The naturally occurring (-)-abyssomicin C and its atropisomer were found to exhibit low micromolar growth inhibition against the relatively fast-growing and non-virulent Mycobacterium smegmatis and the vaccine strain Mycobacterium bovis BCG, while their antipodes were slightly less active. (-)-Abyssomicin C and its atropisomer were particularly efficacious against Mycobacterium tuberculosis H37Rv, exhibiting MIC values of 3.6 and 7.2 mu M, respectively. More specifically, (-)-abyssomicin C was bactericidal. This complex natural product and its analogs, thus, hold promise as chemical tools in the study of M. tuberculosis metabolism. (C) 2010 Elsevier Ltd. All rights reserved.