Identification of Novel Sphydrofuran-Derived Derivatives with Lipid-Lowering Activity from the Active Crude Extracts of Nocardiopsis sp. ZHD001

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2822
• Main Authors: Tian, Yuhong, Jiang, Yongjun, Wen, Zhengshun, Guan, Liping, Ouyang, Xiaokun, Ding, Wanjing, Ma, Zhongjun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Actinomycetes; Animal models; Animals; Biocompatibility; Biological activity; Cardiovascular diseases; Cholesterol; Chromatography; Cytotoxicity; Drug development; Drugs; Glycerol; High density lipoprotein; High fat diet; Hyperlipidemia; Hypolipidemic Agents - therapeutic use; lipid-lowering; Lipids; Low density lipoprotein; Mice; Natural products; NMR; Nocardiopsis; Nocardiopsis sp; Nuclear magnetic resonance; Plant Extracts - chemistry; Simvastatin; sphydrofuran derivatives; structure elucidation; Two dimensional analysis; Weight reduction; structure elucidation; lipid-lowering; sphydrofuran derivatives; Nocardiopsis sp
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.