title: 2-Arylbenzo[b]furan derivatives as potent human lipoxygenase inhibitors.
abstract: 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.
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Li
authors: L
authors: Lang
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Ningning
authors: N
authors: Dong
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Deyan
authors: D
authors: Wu
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Xue
authors: X
authors: Yao
authors: b Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai , China , and.
authors: Weiqiang
authors: W
authors: Lu
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Chen
authors: C
authors: Zhang
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Ping
authors: P
authors: Ouyang
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Jin
authors: J
authors: Zhu
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Yun
authors: Y
authors: Tang
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.|c Department of Chemistry & Chemical Biology , University of New Mexico , Albuquerque , NM , USA.
authors: Wei
authors: W
authors: Wang
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Jian
authors: J
authors: Li
authors: a Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors: Jin
authors: J
authors: Huang
mesh_terms: D031622:Artocarpus / Q000737:chemistry; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008084:Lipoxygenase / Q000302:isolation & purification / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D016859:Lipoxygenase Inhibitors; D008084:Lipoxygenase
keywords: 2-arylbenzo[b]furan; Anti-inflammation; Artocarpus heterophyllus; lipoxygenase; neutrophils