Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site

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dc.contributor.authorDurdağı, Serdar
dc.contributor.authorŞentürk, Murat
dc.contributor.authorEkinci, Deniz
dc.contributor.authorBalaydın, Halis Türker
dc.contributor.authorGöksu, Süleyman
dc.contributor.authorKüfreviolu, Ö. İrfan
dc.contributor.authorInnocenti, Alessio
dc.contributor.authorScozzafava, Andrea
dc.contributor.authorSupuran, Claudiu T.
dc.date.accessioned2025-07-02T13:48:42Z
dc.date.available2025-07-02T13:48:42Z
dc.date.issued2011
dc.departmentAÇÜ, Eğitim Fakültesi, Temel Eğitim Bölümü
dc.description.abstractCarbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic anions, phenols, coumarins (acting as prodrugs) and polyamines. A novel class of CA inhibitors (CAIs), interacting with the CA isozymes I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) in a different manner, is reported here. Kinetic measurements allowed us to identify hydroxy-/methoxy-substituted benzoic acids as well as di-/tri-methoxy benzenes as submicromolar-low micromolar inhibitors of the four CA isozymes. Molecular docking studies of a set of such inhibitors within CA I and II allowed us to understand the inhibition mechanism. This new class of inhibitors binds differently compared to all other classes of inhibitors known to date: they were found between the phenol-binding site and the coumarin-binding site, filling thus the middle of the enzyme cavity. They exploit different interactions with amino acid residues and water molecules from the CA active site compared to other classes of inhibitors, offering the possibility to design CAIs with an interesting inhibition profile compared to the clinically used sulfonamides/sulfamates.
dc.identifier.doi10.1016/j.bmc.2011.01.016
dc.identifier.endpage1389
dc.identifier.issn09680896
dc.identifier.issue4
dc.identifier.pmid21282059
dc.identifier.scopus2-s2.0-79951556617
dc.identifier.scopusqualityQ2
dc.identifier.startpage1381
dc.identifier.urihttps://hdl.handle.net/11494/5648
dc.identifier.volume19
dc.identifier.wosWOS:000287592100002
dc.identifier.wosqualityQ3
dc.indekslendigikaynakScopus
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.institutionauthorBalaydın, Halis Türker
dc.language.isoen
dc.publisherELSEVIER SCIENCE LTD
dc.relation.ispartofBioorganic and Medicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCarbonic anhydrase
dc.subjectDimethoxy-benzene
dc.subjectDocking
dc.subjectEnzyme inhibition
dc.subjectPhenol
dc.subjectPhenolic acid
dc.subjectSulfonamide
dc.titleKinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site
dc.typeArticle

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