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Discovery of Nosiheptide, Griseoviridin, and Etamycin as Potent Anti-Mycobacterial Agents against Mycobacterium avium Complex

1
Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan
2
Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan
3
OP BIO FACTORY Co., Ltd., 5-8 Suzaki, Uruma-shi, Okinawa 904-2234, Japan
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(8), 1495; https://doi.org/10.3390/molecules24081495
Received: 4 April 2019 / Revised: 11 April 2019 / Accepted: 15 April 2019 / Published: 16 April 2019
(This article belongs to the Collection Bioactive Compounds)
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Abstract

Mycobacterium avium complex (MAC) is a serious disease mainly caused by M. avium and M. intracellulare. Although the incidence of MAC infection is increasing worldwide, only a few agents are clinically used, and their therapeutic effects are limited. Therefore, new anti-MAC agents are needed. Approximately 6600 microbial samples were screened for new anti-mycobacterial agents that inhibit the growth of both M. avium and M. intracellulare, and two culture broths derived from marine actinomycete strains OPMA1245 and OPMA1730 had strong activity. Nosiheptide (1) was isolated from the culture broth of OPMA1245, and griseoviridin (2) and etamycin (viridogrisein) (3) were isolated from the culture broth of OPMA1730. They had potent anti-mycobacterial activity against M. avium and M. intracellulare with minimum inhibitory concentrations (MICs) between 0.024 and 1.56 μg/mL. In addition, a combination of 2 and 3 markedly enhanced the anti-mycobacterial activity against both M. avium and M. intracellulare. Furthermore, a combination 2 and 3 had a therapeutic effect comparable to that of ethambutol in a silkworm infection assay with M. smegmatis. View Full-Text
Keywords: nontuberculous mycobacteria; Mycobacterium avium complex; griseoviridin; viridogrisein; etamycin; nosiheptide; antimycobacterial activity; microbial product; marine-derived actinomycete nontuberculous mycobacteria; Mycobacterium avium complex; griseoviridin; viridogrisein; etamycin; nosiheptide; antimycobacterial activity; microbial product; marine-derived actinomycete
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Hosoda, K.; Koyama, N.; Kanamoto, A.; Tomoda, H. Discovery of Nosiheptide, Griseoviridin, and Etamycin as Potent Anti-Mycobacterial Agents against Mycobacterium avium Complex. Molecules 2019, 24, 1495.

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