Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis.

OBJECTIVE: Our aim was to identify natural products with anti-tubercular activity. RESULTS: A set of ~ 500 purified natural product compounds was screened for inhibition against the human pathogen Mycobacterium tuberculosis. A series of cyclic hexapeptides with anti-tubercular activity was identified. Five analogs from a set of sixteen closely related compounds were active, with minimum inhibitory concentrations ranging from 2.3 to 8.9 µM. Eleven structural analogs had no significant activity (MIC > 20 µM) demonstrating structure activity relationship. Sequencing of resistant mutant isolates failed to identify changes accounting for the resistance phenotype.