title: 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII.
abstract: A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC 4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two tested compounds exhibited excellent CA activity profile against the four CA isozymes when compared to the reference drug acetazolamide. Six of the tested compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (Ki < 5 nM) for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed Ki < 10 nM against hCA XII. In addition, they acted as selective CA inhibitors of isoforms IX and XII over the physiological isoforms I and II.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Khloya
authors.affiliation: Chemistry Department, Balikesir University, 10145 Balikesir, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Celik
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.lastname: SitaRam
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: Daniela
authors.initials: D
authors.lastname: Vullo
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 Nutraceutical 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
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India. Electronic address: pksharma@kuk.ac.in.
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Sharma
mesh_terms: D000951:Antigens, Neoplasm / Q000187:drug effects*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry*; D000096926:Benzenesulfonamides
chemical_list: D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D011720:Pyrazoles; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C089226:CA9 protein, human
keywords: Acetazolamide; Benzenesulfonamide; Carbonic anhydrase isoforms I, II, IX, XII; Pyrazole