title: Carbonic anhydrase inhibitors. Novel sulfanilamide/acetazolamide derivatives obtained by the tail approach and their interaction with the cytosolic isozymes I and II, and the tumor-associated isozyme IX.
abstract: A series of sulfonamides has been obtained by reacting sulfanilamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide with omega-chloroalkanoyl chlorides, followed by replacement of the omega-chlorine atom with secondary amines. Tails incorporating heterocyclic amines belonging to the morpholine, piperidine and piperazine ring systems have been attached to these sulfonamides, by means of an alkanoyl-carboxamido linker containing from two to five carbon atoms. The new derivatives prepared in this way were tested as inhibitors of three carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic isozymes CA I and II, and the catalytic domain of the transmembrane, tumor-associated isozyme CA IX. Several low nanomolar CA I and CA II inhibitors were detected both in the aromatic and heterocyclic sulfonamide series, whereas the best hCA IX inhibitors (inhibition constants in the range of 22-35 nM) all belonged to the acetazolamide-like derivatives.
authors.affiliation: Department of Chemistry, Faculty of Science and Arts, Harran University, 63300 Sanliurfa, Turkey. hturkmen@harran.edu.tr
authors.forename: Hasan
authors.initials: H
authors.lastname: Turkmen
authors.forename: Mustafa
authors.initials: M
authors.lastname: Durgun
authors.forename: Serpil
authors.initials: S
authors.lastname: Yilmaztekin
authors.forename: Mahmut
authors.initials: M
authors.lastname: Emul
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000086:Acetazolamide / Q000138:chemical synthesis* / Q000494:pharmacology; D000588:Amines / Q000737:chemistry; D014408:Biomarkers, Tumor; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003600:Cytosol / Q000201:enzymology; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000378:metabolism*; D009025:Morpholines / Q000737:chemistry; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000588:Amines; D014408:Biomarkers, Tumor; D002257:Carbonic Anhydrase Inhibitors; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D009025:Morpholines; D010879:Piperazines; D010880:Piperidines; D013424:Sulfanilamides; D000077489:Piperazine; D000077145:Sulfanilamide; C032727:piperidine; C037574:morpholine; D000086:Acetazolamide