title: Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency.
abstract: Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies.
authors.affiliation: Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Blanco
authors.forename: Antía
authors.initials: A
authors.lastname: Sedes
authors.forename: Antonio
authors.initials: A
authors.lastname: Peón
authors.forename: Heather
authors.initials: H
authors.lastname: Lamb
authors.forename: Alastair R
authors.initials: AR
authors.lastname: Hawkins
authors.forename: Luis
authors.initials: L
authors.lastname: Castedo
authors.forename: Concepción
authors.initials: C
authors.lastname: González-Bello
mesh_terms: D004746:Enoyl-CoA Hydratase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D018716:Molecular Mimicry; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007659:Ketones; D004746:Enoyl-CoA Hydratase