School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
Institute of Marine Biology and Pharmacology, Ocean College, Zhejiang University, Zhoushan 316021, China.
Int J Mol Sci. 2023 Feb 1;24(3):2822. doi: 10.3390/ijms24032822.
Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (-) and one known 2-methyl-4-(1-glycerol)-furan (). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs.
降脂是预防和治疗心血管疾病最有效的方法之一。然而，大多数临床降脂药物都有不良反应，并且在一些复杂的高脂血症患者中无法达到预期的疗效，因此开发安全有效的新型降脂药物具有重要意义。在我们旨在发现海洋放线菌中具有化学新颖性和生物活性的天然产物的项目过程中，我们发现 sp. ZHD001 的有机粗提取物 (OCEs) 在降低高脂饮食喂养的小鼠模型体重增加、降低 LDL-C、TC 和 TG 水平以及提高 HDL-C 水平方面表现出很强的体内疗效。对活性 OCEs 的化学研究导致鉴定出两种新的 sp 氢呋喃衍生化合物 (-) 和一种已知的 2-甲基-4-(1-甘油基)-呋喃 ()。通过分析 HRESIMS、1D 和 2D NMR 光谱数据和 ECD 计算，阐明了它们的结构。在这些化合物中，化合物代表一种新型的重排 sp 氢呋喃衍生衍生物。这些纯化合物的活性评估表明，与辛伐他汀相比，所有化合物在体外均表现出显著的降脂活性和更低的细胞毒性。我们的结果表明，sp 氢呋喃衍生衍生物可能是有前途的降脂药物候选物。
