title: Discovery of potential sorbitol dehydrogenase inhibitors from virtual screening.
abstract: Sorbitol dehydrogenase (SDH) is the second enzyme in the polyol pathway of glucose metabolism and is a possible target for the treatment of the complications of diabetes. In this study the molecular modelling program DOCK was used to analyse 249,071 compounds from the National Cancer Institute Database and predict those with high affinity for SDH. From a total of 21 tested the 7 compounds including flavin adenine dinucleotide disodium hydrate, (+)-Amethopterin, 3-hydroxy-2-napthoic(2-hydroxybenzylidene) hydrazide, folic acid, N-2,4-dinitrophenyl-L-cysteic acid, Vanillin azine and 1H-indole-2,3-dione,5-bromo-6-nitro-1-(2,3,4-tri-O-acetyl-alpha-L-arabinopyranosyl)-(9Cl), were shown to inhibit SDH and displayed IC50 values of 0.192 microM, 1.1 microM, 1.2 microM, 4.5 microM, 5.3 microM, 7 microM and 28 microM, respectively. These compounds may aid the design of pharmaceutical agents for the treatment of diabetes complications.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
authors.forename: Connie
authors.initials: C
authors.lastname: Darmanin
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Carper
authors.forename: Ossama
authors.initials: O
authors.lastname: El-Kabbani
mesh_terms: D003628:Database Management Systems; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007064:L-Iditol 2-Dehydrogenase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D007064:L-Iditol 2-Dehydrogenase