title: Kinetic and in silico studies of hydroxy-based inhibitors of carbonic anhydrase isoforms I and II.
abstract: A series of hydroxy and phenolic compounds have been assayed for the inhibition of two physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic human isozymes I and II. The investigated molecules showed inhibition constants in the range of 1.07-4003 and 0.09-31.5 μM at the hCA I and hCA II enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are compared using three different scoring algorithms, namely Glide/SP, Glide/XP and Glide/IFD. In addition, different ADME (absorption, distribution, metabolism and excretion) analysis was performed. All the examined compounds were found within the acceptable range of pharmacokinetic profiles.
authors: a Department of Chemistry , Istanbul Technical University , Istanbul , Turkey .
authors: Ramin
authors: R
authors: Ekhteiari Salmas
authors: b School of Medicine, Bahcesehir University , Istanbul , Turkey .
authors: Mert
authors: M
authors: Mestanoglu
authors: c Department of Biophysics , School of Medicine, Bahcesehir University , Istanbul , Turkey .
authors: Serdar
authors: S
authors: Durdagi
authors: d Department of Chemistry, Art and Science Faculty , Agri Ibrahim Cecen University , Agri , Turkey , and.
authors: Murat
authors: M
authors: Sentürk
authors: e School of Health, Gumushane University , Gumushane , Turkey.
authors: A Afşin
authors: AA
authors: Kaya
authors: e School of Health, Gumushane University , Gumushane , Turkey.
authors: Elif Çelenk
authors: EÇ
authors: Kaya
mesh_terms: D000465:Algorithms; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D010636:Phenols; D002256:Carbonic Anhydrases
keywords: ADME; CA inhibitors; carbonic anhydrase; molecular docking simulations