title: 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations.
abstract: A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683-4250nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar-nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides.
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., Riga LV-1006, Latvia; Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, 3/7 Paula Valdena Str., Riga LV-1048, Latvia.
authors.forename: Jekaterīna
authors.initials: J
authors.lastname: Ivanova
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., Riga LV-1006, Latvia; Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, 3/7 Paula Valdena Str., Riga LV-1048, Latvia.
authors.forename: Agnese
authors.initials: A
authors.lastname: Balode
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., Riga LV-1006, Latvia. Electronic address: raivis@osi.lv.
authors.forename: Raivis
authors.initials: R
authors.lastname: Žalubovskis
authors.affiliation: Latvian Biomedical Research and Study Center, Rātsupītes 1, LV-1067 Riga, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Leitans
authors.affiliation: Latvian Biomedical Research and Study Center, Rātsupītes 1, LV-1067 Riga, Latvia.
authors.forename: Andris
authors.initials: A
authors.lastname: Kazaks
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Latvian Biomedical Research and Study Center, Rātsupītes 1, LV-1067 Riga, Latvia; Faculty of Biology, Department of Molecular Biology, University of Latvia, Jelgavas 1, LV1004 Riga, Latvia.
authors.forename: Kaspars
authors.initials: K
authors.lastname: Tars
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di ScienzeFarmaceutiche e Nutraceutiche, 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: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D012996:Solutions; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D012996:Solutions; D013449:Sulfonamides; D013876:Thiophenes; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Inhibitor; Mercaptan; Thiophene-2-sulfonamide