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.
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.
J Nat Prod. 2020 May 22;83(5):1646-1657. doi: 10.1021/acs.jnatprod.0c00151. Epub 2020 Apr 23.
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 (-), bearing various nonproteinogenic amino acids, along with ilamycins E () and F (), from a 200 L scale culture of the marine-derived mutant actinomycete SCSIO ZH16 Δ. Importantly, bioassays against H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 μM. The structures of - were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 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.
结核病 (TB) 在过去十年中一直是单一感染源导致死亡的主要原因（比 HIV/AIDS 更致命）。更令人担忧的是，耐多药 (MDR) 和广泛耐药 (XDR) 结核菌株的报告数量急剧增加。显然，需要具有更高疗效和更低毒性的新型抗结核药物。我们在此报告了 12 种新的伊拉霉素类似物，即 ilamycins G-R (-)，它们带有各种非蛋白氨基酸，以及 ilamycins E () 和 F (())，这些化合物是从海洋来源的突变放线菌 SCSIO ZH16 Δ 的 200 L 规模培养物中分离得到的。重要的是，对 H37Rv 的生物测定表明，所有 12 种新化合物均具有抗结核活性，MIC 值范围为 0.0096 至 10 μM。基于 HRESIMS、1D 和 2D NMR 以及 X 射线单晶衍射研究，确定了 - 的结构。此外，化合物 对一组肿瘤人类细胞系表现出中等细胞毒性。根据这些数据，我们可以制定伊拉霉素的抗结核和抗肿瘤活性的暂定结构-活性关系。
