期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 31, 期 -, 页码 98-105出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2016.1220376
关键词
Anti-inflammation; Artocarpus heterophyllus; 2-arylbenzo[b]furan; lipoxygenase; neutrophils
资金
- National Natural Science Foundation of China [21222211, 21372001, 91313303, 81402482]
- Program for New Century Excellent Talents in University [NCET-12-0853]
- Shanghai Committee of Science and Technology [11DZ2260600, 14ZR1411100]
- China Postdoctoral Science Foundation grant [2014M551361, 2015T80415]
- Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [145G28]
- Fundamental Research Funds for the Central Universities
Human lipoxygenases (LOXs) have been emerging as effective therapeutic targets for inflammatory diseases. In this study, we found that four natural 2-arylbenzo[b]furan derivatives isolated from Artocarpus heterophyllus exhibited potent inhibitory activities against human LOXs, including moracin C (1), artoindonesianin B-1 (2), moracin D (3), moracin M (4). In our in vitro experiments, compound 1 was identified as the most potent LOX inhibitor and the moderate subtype selective inhibitor of 12-LOX. Compounds 1 and 2 act as competitive inhibitors of LOXs. Moreover, 1 significantly inhibits LTB4 production and chemotactic capacity of neutrophils, and is capable of protecting vascular barrier from plasma leakage in vivo. In addition, the preliminary structure-activity relationship analysis was performed based on the above four naturally occurring (1-4) and six additional synthetic 2-arylbenzo[b]furan derivatives. Taken together, these 2-arylbenzo[b]furan derivatives, as LOXs inhibitors, could represent valuable leads for the future development of therapeutic agents for inflammatory diseases.
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