@article{He2025, 
author = {Li-Ming He and Xuan Deng and Li-Hua Ni and Shi-Qi Cai and Jinhu Chen and Zejin Liao and Mengke Zhang and Hua Shui and Kong-Kai Zhu and Song Wu and Ping Gao and Ariel M. Sarotti and Kui Hong and Xiao-Yan Wu and You-Sheng Cai},
title = {Penicipyrrolidines A−N, pyrrolidine derivatives with inhibitory effects on EMT and fibroblast activation from the mangrove-derived fungus Penicillium sp. DM27},
year = {2025},
journal = {Marine Life Science & Technology},
volume = {7},
number = {2},
pages = {313-327},
keywords = {Penicillium sp., Pyrrolidine, Pyrrolizidine alkaloids, Renal fibrosis, Fibroblast activation},
url = {https://www.sciopen.com/article/10.1007/s42995-025-00282-0},
doi = {10.1007/s42995-025-00282-0},
abstract = {An investigation of the mangrove-derived fungus Penicillium sp. DM27 led to the isolation of 19 new compounds, including three pairs of piperidinone enantiomers (±)-1, (±)-2, and (±)-3, two pairs of pyrrolidinone enantiomers (±)-4 and (±)-5, and nine pyrrolidine derivatives 6−14. The structures of 1−14 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 11 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 11 could dock ADAM17, showing a high negative binding affinity. Additionally, the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT, while compound 11 suppressed this process. Overall, our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.}
}