海洋来源的青霉属真菌的第一个二聚体吲哚-二萜及其抗肥胖药物的潜力。

IF 5.3 2区 生物学 Q1 MARINE & FRESHWATER BIOLOGY Marine Life Science & Technology Pub Date : 2024-10-08 eCollection Date: 2025-02-01 DOI:10.1007/s42995-024-00253-x
Hui-Fang Du, Lei Li, Ya-Hui Zhang, Xu Wang, Cheng-Yan Zhou, Hua-Jie Zhu, Charles U Pittman, Jia-Wen Shou, Fei Cao
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引用次数: 0

摘要

肥胖已经成为一个世界性的健康问题。从多种真菌中寻找具有抗肥胖活性的天然产物已引起药理学家的关注。本研究首次从产自salsa的海洋真菌Penicillium sp. CF-06中分离到具有罕见的C-20-C-22'连锁的二聚吲哚-二萜A和B(1和2)及其单体(3和4)。通过计算的TDDFT ECD方法确定1-3的绝对构型。首次用单晶x射线衍射方法验证了4的结构。有趣的是,1和2通过下调过氧化物酶体增殖物激活受体γ (PPARγ)和CCAAT/增强子结合蛋白α (C/EBPα)蛋白的表达,对3T3-L1脂肪细胞的分化有显著影响,而单体3和4没有表现出活性。分子对接结果解释了二聚体1与PPARγ的相互作用强于单体3与PPARγ的相互作用机制。我们的研究可以为发现抗肥胖药物提供新的见解。补充信息:在线版本包含补充资料,提供地址为10.1007/s42995-024-00253-x。
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The first dimeric indole-diterpenoids from a marine-derived Penicillium sp. fungus and their potential for anti-obesity drugs.

Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20-C-22' linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1-3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-024-00253-x.

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来源期刊
Marine Life Science & Technology
Marine Life Science & Technology MARINE & FRESHWATER BIOLOGY-
CiteScore
9.60
自引率
10.50%
发文量
58
期刊介绍: Marine Life Science & Technology (MLST), established in 2019, is dedicated to publishing original research papers that unveil new discoveries and theories spanning a wide spectrum of life sciences and technologies. This includes fundamental biology, fisheries science and technology, medicinal bioresources, food science, biotechnology, ecology, and environmental biology, with a particular focus on marine habitats. The journal is committed to nurturing synergistic interactions among these diverse disciplines, striving to advance multidisciplinary approaches within the scientific field. It caters to a readership comprising biological scientists, aquaculture researchers, marine technologists, biological oceanographers, and ecologists.
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