Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis
Sheo B Singh1,2, Joshua Odingo3, Mai A Bailey3
1Merck & Co., Inc., Infectious Diseases, 770 Sumneytown Pike, West Point, PA, 19486, USA.
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.
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Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
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