AUTHOR=Li Jun , Liu Zhiyong , Hong Mingye , Sun Changli , Zhang Tianyu , Zhang Hua , Ju Jianhua , Ma Junying 

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

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.774555

DOI=10.3389/fchem.2021.774555

ISSN=2296-2646

ABSTRACT=<p>Tuberculosis (TB) is still a global disease threatening people’s lives. With the emergence of multi-drug-resistant <italic>Mycobacterium tuberculosis</italic> 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 <italic>M. tuberculosis</italic> and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain <italic>Streptomyces atratus</italic> SCSIO ZH16 Δ<italic>ilaR</italic>, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1–NJL18, <bold>1</bold>–<bold>18</bold>). Our study reveals that four of ilamycin NJLs (<bold>1, 6, 8</bold>, and <bold>10</bold>) have slightly stronger anti-TB activities against <italic>Mtb</italic> 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 (<bold>1</bold>). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.</p>