TY  - JOUR
AU  - He, Li-Ming
AU  - Deng, Xuan
AU  - Ni, Li-Hua
AU  - Cai, Shi-Qi
AU  - Chen, Jinhu
AU  - Liao, Zejin
AU  - Zhang, Mengke
AU  - Shui, Hua
AU  - Zhu, Kong-Kai
AU  - Wu, Song
AU  - Gao, Ping
AU  - Sarotti, Ariel M.
AU  - Hong, Kui
AU  - Wu, Xiao-Yan
AU  - Cai, You-Sheng
PY  - 2025
TI  - Penicipyrrolidines A−N, pyrrolidine derivatives with inhibitory effects on EMT and fibroblast activation from the mangrove-derived fungus Penicillium sp. DM27
JO  - Marine Life Science & Technology
SN  - 2096-6490
SP  - 313
EP  - 327
VL  - 7
IS  - 2
AB  - 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.
UR  - https://doi.org/10.1007/s42995-025-00282-0
DO  - 10.1007/s42995-025-00282-0