Journal
MARINE DRUGS
Volume 10, Issue 3, Pages 639-654Publisher
MDPI AG
DOI: 10.3390/md10030639
Keywords
Streptomyces xiamenensis; mangrove; benzopyran; fibroblast; anti-fibrosis; anti-contractile capacity
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Funding
- National Science Foundation of China [30901845, 91029738, 3082105]
- National Basic Research Program of China 973 [2012CB72100]
- State Key Laboratory of Oncogenes and Related Genes [90-10-11]
- SRF for ROCS, SEM SHSTC [10PJ1405200]
- SHEC [SOS-0900000171]
- Research Fund for the New Teacher Program of Higher Education of China [20090001120047]
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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.
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