title: Synthesis and activity of a new series of (Z)-3-phenyl-2-benzoylpropenoic acid derivatives as aldose reductase inhibitors.
abstract: During the course of studies directed towards the discovery of novel aldose reductase inhibitors for the treatment of diabetic complications, we synthesized a series of new (Z)-3-phenyl-2-benzoylpropenoic acid derivatives and tested their in vitro inhibitory activities on rat lens aldose reductase. Of these compounds, (Z)-3-(3,4-dihydroxyphenyl)-2-(4-methylbenzoyl)propenoicacid (3k) was identified as the most potent inhibitor, with an IC50 of 0.49 microM. The theoretical binding mode of 3k was obtained by simulation of its docking into the active site of the human aldose reductase crystal structure.
authors.affiliation: Key Laboratory of New Drugs Design and Discovery of Liaoning Province, Shenyang Pharmaceutical University, Shenyang 110016, PR China. sjwang_99@yahoo.com.cn
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Wang
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Yan
authors.forename: Dong
authors.initials: D
authors.lastname: Hao
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Niu
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011422:Propionates / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001565:Benzoates; D004791:Enzyme Inhibitors; D011422:Propionates; C400972:benzoylpropionic acid; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase