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

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• 作者：Masayoshi Arai ; Yoshi Yamano ; Kentaro Kamiya ; Andi Setiawan…
• 刊名：Journal of Natural Medicines
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：70
• 期：3
• 页码：467-475
• 全文大小：5,395 KB
• 刊物主题：Pharmacology/Toxicology; Plant Sciences; Complementary & Alternative Medicine; Medicinal Chemistry; Pharmacy;
• 出版者：Springer Japan
• ISSN：1861-0293
• 卷排序：70

文摘

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.KeywordsMelophlinMarine spongeAntibioticTuberculosisCarbon sourceDormant