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

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 2.3-8.9 M. Eleven structural analogs had no significant activity (MIC > 20 M) demonstrating structure activity relationship. Sequencing of resistant mutant isolates failed to identify changes accounting for the resistance phenotype.