Penicipyrrolidines A-N, pyrrolidine derivatives with inhibitory effects on EMT and fibroblast activation from the mangrove-derived fungus sp. DM27.

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.