2. Academic Validation
  3. Antitubercular Ilamycins from Marine-Derived Streptomyces atratus SCSIO ZH16 Δ ilaR

Antitubercular Ilamycins from Marine-Derived Streptomyces atratus SCSIO ZH16 Δ ilaR

  • J Nat Prod. 2020 May 22;83(5):1646-1657. doi: 10.1021/acs.jnatprod.0c00151.
Changli Sun 1,  Zhiyong Liu 2 3,  Xiangcheng Zhu 4,  Zhiying Fan 4,  Xuanmei Huang 5,  Qiaoling Wu 1 6,  Xiaohong Zheng 1,  Xiangjing Qin 1,  Tianyu Zhang 2 3,  Hua Zhang 5,  Jianhua Ju 1 6,  Junying Ma 1
Affiliations

Affiliations

  • 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, 164 West Xingang Road, Guangzhou 510301, China.
  • 2 Tuberculosis Research Laboratory, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Huangpu District, Guangzhou 510530, China.
  • 3 Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Guangzhou 510530, China.
  • 4 Xiangya International Academy of Translational Medicine, Central South University; National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, 172 Tongzipo Road, Changsha, Hunan 410013, China.
  • 5 Guangdong Province Key Laboratory of Medical Molecular Diagnostics, Institute of Laboratory Medicine, Guangdong Medical University, 1 Xincheng Road, Dongguan 523808, China.
  • 6 College of Oceanology, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 110039, China.
PMID: 32324401 DOI: 10.1021/acs.jnatprod.0c00151
Abstract

Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (1-12), bearing various nonproteinogenic Amino acids, along with ilamycins E1 (13) and F (14), from a 200 L scale culture of the marine-derived mutant actinomycete Streptomyces atratus SCSIO ZH16 ΔilaR. Importantly, bioassays against Mycobacterium tuberculosis H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 μM. The structures of 1-12 were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 10 was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.

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