title: Salicylaldoxime derivatives as new leads for the development of carbonic anhydrase inhibitors.
abstract: New compounds containing a novel zinc binding group (salicylaldoxime system) were identified as effective inhibitors of carbonic anhydrases (CAs). This structural motif seems to bind the catalytic zinc ion of CAs, revealing itself as a new valid alternative to the sulfonamide group. Computational procedures were used to investigate the binding mode of this class of compounds, within the active site of CAII. This study suggests that the salicylaldoxime moiety binds the zinc ion through the oxime oxygen atom that also forms an H-bond with T199. The results herein obtained will allow the development of new CA-inhibitors bearing the salicylaldoxime moiety.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Pisa, Via Bonanno 6, 56126 Pisa, Italy. tuccinardi@farm.unipi.it
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Carlotta
authors.initials: C
authors.lastname: Granchi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001665:Binding Sites; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D062105:Molecular Docking Simulation; D010091:Oximes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011789:Quantum Theory; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D010091:Oximes; C005704:salicylaldoxime; D002256:Carbonic Anhydrases; D015032:Zinc