Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp

[Display omitted] In the course of our search for anti-dormant Mycobacterial substances, nybomycin (1) was re-discovered from the culture broth of a marine-derived Streptomyces sp. on the bioassay-guided separation. Compound 1 showed anti-microbial activity against Mycobacterium smegmatis and Mycoba...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2015-07, Vol.23 (13), p.3534-3541
Hauptverfasser: Arai, Masayoshi, Kamiya, Kentaro, Pruksakorn, Patamaporn, Sumii, Yuji, Kotoku, Naoyuki, Joubert, Jean-Pierre, Moodley, Prashini, Han, Chisu, Shin, Dayoung, Kobayashi, Motomasa
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Sprache:eng
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Zusammenfassung:[Display omitted] In the course of our search for anti-dormant Mycobacterial substances, nybomycin (1) was re-discovered from the culture broth of a marine-derived Streptomyces sp. on the bioassay-guided separation. Compound 1 showed anti-microbial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG with the MIC of 1.0μg/mL under both actively growing aerobic conditions and dormancy inducing hypoxic conditions. Compound 1 is also effective to Mycobacterium tuberculosis including the clinically isolated strains. The mechanistic analysis indicated that 1 bound to DNA and induces a unique morphological change to mycobacterial bacilli leading the bacterial cell death.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2015.04.033