Semi-Synthesis of Marine-Derived Ilamycin F Derivatives and Their Antitubercular Activities

Frontiers in Chemistry

Jianhua Ju²  Junying Ma²  Mingye Hong³  Hua Zhang³  Jun Li⁴  Changli Sun⁴  Zhiyong Liu⁵  Tianyu Zhang⁵ 

[1] CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China;College of Oceanology, University of Chinese Academy of Sciences, Qingdao, China;Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, China;Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China;Tuberculosis Research Laboratory, State Key Laboratory of Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;

关键词: streptomycetes;    cyclopeptide;    antitubercular activity;    ilamycin;    semi-synthesis;    derivatization;   

DOI  :  10.3389/fchem.2021.774555

来源: DOAJ

【 摘 要 】

Tuberculosis (TB) is still a global disease threatening people’s lives. With the emergence of multi-drug-resistant Mycobacterium tuberculosis the prevention and control of tuberculosis faces new challenges, and the burden of tuberculosis treatment is increasing among the world. Ilamycins are novel cyclopeptides with potent anti-TB activities, which have a unique target protein against M. tuberculosis and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain Streptomyces atratus SCSIO ZH16 ΔilaR, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1–NJL18, 1–18). Our study reveals that four of ilamycin NJLs (1, 6, 8, and 10) have slightly stronger anti-TB activities against Mtb H37Rv (minimum inhibitory concentration, 1.6–1.7 μM) compared with that of ilamycin F on day 14th, but obviously display more potent activities than ilamycin F on day 3rd, indicating anti-TB activities of these derivatives with fast-onset effect. In addition, cytotoxic assays show most ilamycin NJLs with low cytotoxicity except ilamycin NJL1 (1). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.

【 授权许可】

Unknown