title: Azastilbenes: a cut-off to p38 MAPK inhibitors.
abstract: Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Box 576, SE-75123 Uppsala, Sweden.
authors.forename: Jia-Fei
authors.initials: JF
authors.lastname: Poon
authors.forename: John Patrick
authors.initials: JP
authors.lastname: Alao
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Peter
authors.initials: P
authors.lastname: Dinér
mesh_terms: D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001372:Aza Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013267:Stilbenes; D048051:p38 Mitogen-Activated Protein Kinases