title: Kinetic and in silico analysis of thiazolidin-based inhibitors of α-carbonic anhydrase isoenzymes.
abstract: Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic anions, phenols, salicylic acid derivatives (acting as drug or prodrugs). A novel class of CA inhibitors (CAIs), interacting with the CA isozymes I and II (cytosolic) in a different manner, is reported here. Kinetic measurements allowed us to identify thiazolidin-based compounds as submicromolar-low micromolar inhibitors of these two CA isozymes. Molecular docking studies of a set of such inhibitors within CA I and II active site allowed us to understand the inhibition mechanism. This new class of inhibitors bind differently compared to other classes of inhibitors known to date: they were found between the phenol-binding site, filling thus the middle of the enzyme cavity.
authors.affiliation: Ondokuz Mayis University, Faculty of Agriculture, Department of Agricultural Biotechnology, Samsun, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.forename: İsmail
authors.initials: İ
authors.lastname: Fidan
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Şeniz
authors.initials: Ş
authors.lastname: Kaban
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013844:Thiazoles; D002256:Carbonic Anhydrases