戊环吡咯烷A - N，来自红树林衍生真菌sp. DM27的对上皮-间质转化和成纤维细胞活化具有抑制作用的吡咯烷衍生物。
Penicipyrrolidines A-N, pyrrolidine derivatives with inhibitory effects on EMT and fibroblast activation from the mangrove-derived fungus sp. DM27.
作者信息
He Li-Ming, Deng Xuan, Ni Li-Hua, Cai Shi-Qi, Chen Jinhu, Liao Zejin, Zhang Mengke, Shui Hua, Zhu Kong-Kai, Wu Song, Gao Ping, Sarotti Ariel M, Hong Kui, Wu Xiao-Yan, Cai You-Sheng
机构信息
Department of Nephrology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 China.
出版信息
Mar Life Sci Technol. 2025 Apr 24;7(2):313-327. doi: 10.1007/s42995-025-00282-0. eCollection 2025 May.
UNLABELLED
An investigation of the mangrove-derived fungus sp. DM27 led to the isolation of 19 new compounds, including three pairs of piperidinone enantiomers ( ±)-, ( ±)-, and ( ±)-, two pairs of pyrrolidinone enantiomers ( ±)- and ( ±)-, and nine pyrrolidine derivatives -. The structures of - were elucidated through NMR and HRESIMS analysis, coupled with experimental and calculated ECD spectroscopy and the modified Mosher method. Quantitative real time PCR and Western bolt analyses revealed that blocked EMT in TGF-β1-treated HK-2 cells and suppressed fibroblast activation in TGF-β1-stimulated NIH-3T3 cells. Molecular simulations demonstrated that compound could dock ADAM17, showing a high negative binding affinity. Additionally, the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT, while compound suppressed this process. Overall, our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42995-025-00282-0.
未标记
对源自红树林的真菌sp. DM27进行的一项研究导致分离出19种新化合物，包括三对哌啶酮对映体(±)-、(±)-和(±)-，两对吡咯烷酮对映体(±)-和(±)-，以及九种吡咯烷衍生物-。通过核磁共振和高分辨电喷雾电离质谱分析，结合实验和计算的电子圆二色光谱以及改良的莫舍尔方法，阐明了-的结构。定量实时聚合酶链反应和蛋白质免疫印迹分析表明，在转化生长因子-β1处理的HK-2细胞中阻断上皮-间质转化，并在转化生长因子-β1刺激的NIH-3T3细胞中抑制成纤维细胞活化。分子模拟表明化合物可以与解聚素金属蛋白酶17对接，显示出高负结合亲和力。此外，通过慢病毒感染过表达解聚素金属蛋白酶17引发肾小管上皮-间质转化，而化合物抑制了这一过程。总体而言，我们的研究表明吡咯烷衍生物可能是治疗肾纤维化疾病的潜在治疗剂。
补充信息
在线版本包含可在10.1007/s42995-025-00282-0获取的补充材料。
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