title: Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII.
abstract: Imine derivatives were obtained by condensation of sulfanilamide with substituted aromatic aldehydes. The Schiff bases were thereafter reduced with sodium borohydride, leading to the corresponding amines, derivatives of 4-sulfamoylphenyl-benzylamine. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). We noted that the compounds incorporating secondary amine moieties showed a better inhibitory activity against all CA isozymes compared to the corresponding Schiff bases. Low nanomolar CA II, IX and XII inhibitors were detected, whereas the activity against hCA I was less potent. The secondary amines incorporating sulfonamide or similar zinc-binding groups, poorly investigated chemotypes for designing metalloenzyme inhibitors, may offer interesting opportunities in the field due to the facile preparation and possibility to explore a vast chemical space.
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Harran University, 63190 Sanliurfa, Turkey. Electronic address: mustafadurgun@harran.edu.tr.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Durgun
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Harran University, 63190 Sanliurfa, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Turkmen
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D012545:Schiff Bases; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Isoform; Schiff base; Secondary amine; Sulfonamide