title: B-Ring-modified and/or 5-demethylated nobiletin congeners: inhibitory activity against pro-MMP-9 production.
abstract: Three metabolites and 12 analogues of nobiletin (1) were synthesized. Whereas nobiletin derivatives 2-4 inhibited pro-MMP-9 production similarly in both PMA- and TNF-α-stimulated human lens epithelial cells, the 2'-hydroxylated analogue 5a exerted marked inhibitory effects (IC(50): 0.4 μM) on PMA-treated cells, which were 170-fold more potent than those on TNF-α-treated cells. This activity may be closely related to PKC-mediated transcriptional regulation of pro-MMP-9.
authors: School of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Midori-ku, Sagamihara, Kanagawa 252-5195, Japan. ostr@pharm.teikyo-u.ac.jp
authors: Tetsuta
authors: T
authors: Oshitari
authors: Yuji
authors: Y
authors: Okuyama
authors: Yoshiki
authors: Y
authors: Miyata
authors: Hiroshi
authors: H
authors: Kosano
authors: Hideyo
authors: H
authors: Takahashi
authors: Hideaki
authors: H
authors: Natsugari
mesh_terms: D002460:Cell Line; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004792:Enzyme Precursors; D047309:Flavones; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; C008661:nobiletin; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate