Identification and Characterization of an Anti-Fibrotic Benzopyran Compound Isolated from Mangrove-Derived Streptomyces xiamenensis

• Published in: Marine drugs Vol. 10; no. 3; pp. 639 - 654
• Main Authors: Xu, Min-Juan, Liu, Xiao-Jin, Zhao, Yi-Lei, Liu, Dong, Xu, Zhen-Hao, Lang, Xiao-Meng, Ao, Ping, Lin, Wen-Han, Yang, Song-Lin, Zhang, Zhi-Gang, Xu, Jun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2012; MDPI
• Subjects: anti-contractile capacity; anti-fibrosis; benzopyran; Benzopyrans - isolation & purification; Benzopyrans - pharmacology; Biological effects; Carbonyl compounds; Cell Adhesion - drug effects; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Chromatography, High Pressure Liquid; Collagen - chemistry; fibroblast; Fibroblasts - drug effects; Fibrosis - drug therapy; Geologic Sediments - microbiology; Humans; Hydrolysis; Indicators and Reagents; Leukemia; Magnetic Resonance Spectroscopy; mangrove; Marine; Molecular Conformation; Streptomyces; Streptomyces - growth & development; Streptomyces - metabolism; Streptomyces xiamenensis; Trees - microbiology; Xiamenensis; anti-contractile capacity; anti-fibrosis; fibroblast; mangrove; benzopyran; Streptomyces xiamenensis
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md10030639

An anti-fibrotic compound produced by Streptomyces xiamenensis, found in mangrove sediments, was investigated for possible therapeutic effects against fibrosis. The compound, N-[[3,4-dihydro-3S-hydroxy-2S-methyl-2-(4¢R-methyl-3¢S-pentenyl)-2H-1-benzopyran-6-yl]carbonyl]-threonine (1), was isolated from crude extracts and its structure, including the absolute configuration was determined by extensive spectroscopic data analyses, Mosher’s method, Marfey’s reagent and quantum mechanical calculations. In terms of biological effects, this compound inhibits the proliferation of human lung fibroblasts (WI26), blocks adhesion of human acute monocytic leukemia cells (THP-1) to a monolayer of WI26 cells, and reduces the contractile capacity of WI26 cells in three-dimensional free-floating collagen gels. Altogether, these data indicate that we have identified a bioactive alkaloid (1) with multiple inhibitory biological effects on lung excessive fibrotic characteristics, that are likely involved in fibrosis, suggesting that this molecule might indeed have therapeutic potential against fibrosis.