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19.05.2016 | Original Paper | Ausgabe 3/2016

Journal of Natural Medicines 3/2016

Anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of Melophlus sp.

Zeitschrift:
Journal of Natural Medicines > Ausgabe 3/2016
Autoren:
Masayoshi Arai, Yoshi Yamano, Kentaro Kamiya, Andi Setiawan, Motomasa Kobayashi
Wichtige Hinweise
This article is dedicated to Professor Satoshi Ōmura in celebration of his 2015 Nobel Prize.
M. Arai and Y. Yamano contributed equally to this work.

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. In addition, the requirement for long-term therapy to cure TB complicates treatment of the disease. One of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of TB is that M. tuberculosis has the ability to persist in a dormant state. We therefore established a new screening system to search for substances with activity against dormant mycobacteria using M. smegmatis and M. bovis BCG cultivated in medium containing propionate as sole carbon source to induce dormancy. Subsequently, melophlins A (1), G (2), H (3), and I (4), tetramic acid derivatives, were re-discovered from the Indonesian marine sponge of Melophlus sp. as anti-dormant mycobacterial substances. Moreover, target analysis of melophlin A indicated that it targeted the BCG1083 protein of putative exopolyphosphatase and the BCG1321c protein of diadenosine 5′,5‴-P1,P4-tetraphosphate phosphorylase.

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