Thiazomycin, nocathiacin and analogs show strong activity against clinical strains of drug-resistant Mycobacterium tuberculosis.

Autor: Singh SB; Discovery Chemistry, MRL, Merck & Co., Inc., Kenilworth, NJ, USA., Xu L; Discovery Chemistry, MRL, Merck & Co., Inc., Rahway, NJ, USA., Meinke PT; Discovery Chemistry, MRL, Merck & Co., Inc., Rahway, NJ, USA., Kurepina N; Public Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA., Kreiswirth BN; Public Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA., Olsen DB; Antibacterial Discovery, MRL, Merck & Co., Inc., West Point, PA, USA., Young K; Antibacterial Discovery, MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
Jazyk: angličtina
Zdroj: The Journal of antibiotics [J Antibiot (Tokyo)] 2017 May; Vol. 70 (5), pp. 671-674. Date of Electronic Publication: 2017 Jan 18.
DOI: 10.1038/ja.2016.165
Abstrakt: Thiazolyl peptides are a class of natural products with potent Gram-positive antibacterial activities. Lack of aqueous solubility precluded this class of compounds from advancing to clinical evaluations. Nocathiacins and thiazomycins are sub-classes of thiazolyl peptides that are endowed with structural features amenable for chemical modifications. Semi-synthetic modifications of nocathiacin led to a series of analogs with improved water solubility, while retaining potency and antibacterial spectrum. We studied the activities of a selection of two natural products (nocathiacin and thiazomycin) as well as seven polar semi-synthetic analogs against twenty clinical strains of Mycobacterium tuberculosis with MDR phenotypes. Two compounds show useful activity against H37Rv strain with MIC values ⩽1 μM, two (⩽0.5 μm) and three (⩽10 μm). These two derivatives showed MIC values ⩽2.5 μm against most of the 20 MDR strains regardless their resistance profile. Specifically, these lack cross-resistance to rifampicin, isoniazid and moxifloxacin.
Databáze: MEDLINE
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