Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis.
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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 8.9M. Eleven structural analogs had no significant activity (MIC>20M) demonstrating structure activity relationship. Sequencing of resistant mutant isolates failed to identify changes accounting for the resistance phenotype.
author list (cited authors)
Singh, S. B., Odingo, J., Bailey, M. A., Sunde, B., Korkegian, A., O'Malley, T., ... Parish, T.
complete list of authors
Singh, Sheo B||Odingo, Joshua||Bailey, Mai A||Sunde, Bjorn||Korkegian, Aaron||O'Malley, Theresa||Ovechkina, Yulia||Ioerger, Thomas R||Sacchettini, James C||Young, Katherine||Olsen, David B||Parish, Tanya