title: Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme.
abstract: In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn(2+) ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn(2+) ion.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University , Fatih, Istanbul , Turkey .
authors.forename: Atilla
authors.initials: A
authors.lastname: Akdemir
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry; D001665:Binding Sites; D024401:Carbonic Anhydrase I / Q000737:chemistry; D024402:Carbonic Anhydrase II / Q000737:chemistry; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D005029:Ethylenediamines; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014867:Water; C011452:disalicylaldehyde ethylenediamine; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; D015032:Zinc
keywords: Carbonic anhydrase inhibitor; docking; salen; tetrahydrosalen