title: Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.
abstract: A series of pyrazolylpyrazolines was designed, synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against cytosolic human (h) isozymes hCA I and hCA II as well as transmembrane tumor associated isozymes, hCA IX and hCA XII. All the tested compounds exhibited an excellent CA activity profile against hCA I, hCA II and hCA XII when compared to the reference drug acetazolamide (AZA). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Khloya
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.forename: Sita
authors.initials: S
authors.lastname: Ram
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), 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: D000086:Acetazolamide / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000187:drug effects; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000201:enzymology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; D000086:Acetazolamide
keywords: Acetazolamide; Carbonic anhydrase isoforms I, II, IX, XII; Pyrazoles