title: Inhibitory effect of ursolic acid derivatives on recombinant human aldose reductase.
abstract: Aldose reductase (AR) is the first enzyme in the polyol pathway. AR has been reported to play an important role in the pathogenesis of diabetic complications. Ursolic acid and fourteen synthetic derivatives with ursane skeleton were tested for recombinant human aldose reductase (rhAR) inhibitory activity for development of diabetic complications. Among them, N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) showed most potent rhAR inhibitory activity in vitro. Inhibition mode of N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) was tested uncompetitively by kinetic analysis using the Lineweaver-Burk plots. Ursolic acid derivative N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid is able to inhibit rhAR uncompetitively and could be offered as a lead compound for AR inhibition.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340, Gangwon-do, Republic of Korea.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Lee
authors.forename: S A
authors.initials: SA
authors.lastname: Popov
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: A V
authors.initials: AV
authors.lastname: Shpatov
authors.forename: T P
authors.initials: TP
authors.lastname: Kukina
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Kang
authors.forename: Cheol-Ho
authors.initials: CH
authors.lastname: Pan
authors.forename: Byung Hun
authors.initials: BH
authors.lastname: Um
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D048909:Diabetes Complications / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000449:Aldehyde Reductase; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D014315:Triterpenes; D000097245:Ursolic Acid; C570767:N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid