Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
Mar Drugs. 2022 Feb 28;20(3):178. doi: 10.3390/md20030178.
One new depsidone derivative, aspergillusidone H (), along with seven known biosynthetically related chlorinated polyketides, were obtained from the Beibu Gulf coral-derived fungus GXIMD 02505. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. Notably, the X-ray crystal structure of and the previously unknown absolute configuration of assigned by ECD calculations, are described here for the first time. Compounds -, and exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 μM. In addition, the two potent inhibitors ( and ) dose-dependently suppressed RANKL-induced osteoclast differentiation without any evidence of cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitory activity for the metabolites of these kinds. Besides, compounds , , , and - showed inhibitory activity against marine biofilm-forming bacteria, methicillin-resistant , , , and , with their MIC values ranging from 2 to 64 μg/mL. These findings provide a basis for further development of chlorinated polyketides as potential inhibitors of osteoclast differentiation and/or for use as anti-fouling agents.
从北部湾珊瑚来源的真菌 GXIMD 02505 中获得了一个新的去甲二萜衍生物 Aspergillusidone H ()，以及七个已知的生物合成相关的氯化聚酮。通过全面的物理化学和光谱数据分析确定了它们的结构。值得注意的是，首次描述了通过 X 射线晶体结构和以前未知的通过 ECD 计算确定的绝对构型。化合物 - ， 和 对 20 μM LPS 诱导的 RAW 264.7 巨噬细胞中的 NF-κB 具有抑制作用。此外，两种有效的抑制剂（和 ）在不具有骨髓巨噬细胞细胞（BMMs）毒性的情况下，剂量依赖性地抑制了 RANKL 诱导的破骨细胞分化。这是这些代谢物具有破骨细胞分化抑制活性的首次报道。此外，化合物 ， ， ， 和 - 对海洋生物膜形成细菌，耐甲氧西林 ， ， ， 和 具有抑制活性，其 MIC 值范围为 2 至 64 μg/mL。这些发现为进一步开发作为潜在破骨细胞分化抑制剂的氯化聚酮或作为防污剂提供了依据。
