title: Carbonic anhydrase inhibitors: Design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulfonamide derivatives.
abstract: The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315μM for hCA I and of 18.31-143.8μM against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitrophenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
authors.affiliation: Gebze Technical University, Chemistry Department, 41400 Gebze, Kocaeli, Turkey.
authors.forename: İsmail
authors.initials: İ
authors.lastname: Fidan
authors.affiliation: Bahcesehir University, Medicinal Faculty, Department of Biophysics, 34349 Istanbul, Turkey.
authors.forename: Ramin Ekhteiari
authors.initials: RE
authors.lastname: Salmas
authors.affiliation: Yalova University, Engineering Faculty, Department of Polymer Engineering, 77100 Yalova, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Arslan
authors.affiliation: Ağrı İbrahim Çeçen University, Science and Art Faculty, Chemistry Department, 04100 Ağrı, Turkey. Electronic address: senturkm@gmail.com.
authors.forename: Murat
authors.initials: M
authors.lastname: Şentürk
authors.affiliation: Bahcesehir University, Medicinal Faculty, Department of Biophysics, 34349 Istanbul, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.affiliation: Ondokuz Mayıs University, Faculty of Agriculture, Department of Agricultural Biotechnology, 55139 Samsun, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.affiliation: Ağrı İbrahim Çeçen University, School of Health Services, 04100 Ağrı, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Şentürk
authors.affiliation: Fatih University, Science and Art Faculty, Chemistry Department, 34500 Istanbul, Turkey.
authors.forename: Sedat
authors.initials: S
authors.lastname: Coşgun
authors.affiliation: University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D057075:Enzyme Assays; D004912:Erythrocytes; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010648:Phenylacetates / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D010648:Phenylacetates; D013449:Sulfonamides; D010649:Phenylalanine; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C118008:4-nitrophenylacetic acid; D005998:Glycine
keywords: Carbonic anhydrase; Docking; Enzyme inhibitor; Glycine; Phenylalanine; Sulfonamide