PDF(Pubmed)
Abstract：
Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1-4), along with seven known analogs (5-11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2-128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.
摘要：
红树林衍生的放线菌代表了药物发现中新型生物活性天然产物的丰富来源。在这项研究中,四种新的多烯大环内酯类抗生素anti霉素B-E（1-4），连同七种已知的类似物（5-11），从红树链霉菌GXIMD06359的发酵液中分离。使用半制备型HPLC和SephadexLH-20凝胶过滤纯化来自该菌株的所有化合物,同时遵循抗真菌活性指导的分级分离。它们的结构通过光谱技术阐明，包括UV，HR-ESI-MS,和NMR。除化合物2外,这些化合物对马尔尼菲塔拉霉素表现出广谱抗真菌活性,最小抑制浓度(MIC)值在2-128μg/mL范围内。这是由S.hiroshimensis生产的多烯衍生物作为抗马内菲的生物活性化合物的首次报道。体外研究表明，化合物1对马尔尼菲的抗真菌活性明显强于其他新化合物，化合物1的抗真菌机制可能与细胞膜破裂有关，导致线粒体功能障碍，导致细胞内生物成分的泄漏，随后,细胞死亡。一起来看,本研究为复方1防治塔拉真菌病提供了依据。
