title: In vitro inhibition of lens aldose reductase by (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid in enzyme preparations isolated from diabetic rats.
abstract: (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid (compound 1), a novel aldose reductase inhibitor, was assayed for efficacy and selectivity to inhibit rat lens aldose reductase under in vitro conditions by using enzyme preparations obtained from diabetic animals. The inhibitory efficiency was characterized by IC(50) in micromolar region. Enzyme kinetics analysis revealed uncompetitive type of inhibition, both in relation to the D,L-glyceraldehyde substrate and to the NADPH cofactor. In testing for selectivity, comparisons to rat kidney aldehyde reductase, an enzyme with the highest homology to aldose reductase, was used. The inhibition selectivity of the compound tested was characterized by selectivity factor around 20 and was even slightly improved under conditions of prolonged experimental diabetes. These findings were identical with those in the control rats. To conclude, the inhibitory mode, efficacy and selectivity of compound 1, a novel aldose reductase inhibitor, was preserved even under the conditions of prolonged STZ-induced experimental diabetes of rats.
authors.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 84104 Bratislava 4, Slovakia.
authors.forename: P O
authors.initials: PO
authors.lastname: Djoubissie
authors.forename: V
authors.initials: V
authors.lastname: Snirc
authors.forename: R
authors.initials: R
authors.lastname: Sotnikova
authors.forename: J
authors.initials: J
authors.lastname: Zurova
authors.forename: Z
authors.initials: Z
authors.lastname: Kyselova
authors.forename: S
authors.initials: S
authors.lastname: Skalska
authors.forename: A
authors.initials: A
authors.lastname: Gajdosik
authors.forename: V
authors.initials: V
authors.lastname: Javorkova
authors.forename: J
authors.initials: J
authors.lastname: Vlkovicova
authors.forename: N
authors.initials: N
authors.lastname: Vrbjar
authors.forename: M
authors.initials: M
authors.lastname: Stefek
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000201:enzymology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D007908:Lens, Crystalline / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: C519133:(2-benzyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole-8-yl)-acetic acid; D000085:Acetates; D007211:Indoles; D013311:Streptozocin; D000449:Aldehyde Reductase