title: Benzenesulfonamide bearing imidazothiadiazole and thiazolotriazole scaffolds as potent tumor associated human carbonic anhydrase IX and XII inhibitors.
abstract: Two series of 20 novel heterocyclic compounds, imidazothiadiazoles (3a-3j) and thiazolotriazoles (4a-4j) bearing benzenesulfonamide moiety were synthesized in order to investigate the inhibition potential of both scaffolds against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). Against human isoform hCA I, compounds 3j, 4a-4c, and 4j showed better inhibition potential (Ki<100nM) than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed moderate inhibition with the exception of 3a which showed nearly two fold better profile compared to AZA. Against hCA IX, all the compounds showed moderate inhibitory potential than AZA, whereas against hCA XII, compounds 3a-3c showed better inhibitory potential compared to AZA.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
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: Silvia
authors.initials: S
authors.lastname: Bua
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; Istituto di Bioscienze e Biorisorse, CNR, Via PietroCastellino 111, 80131 Napoli, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Del Prete
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via PietroCastellino 111, 80131 Napoli, Italy.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
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: D000951:Antigens, Neoplasm / Q000378:metabolism; D000071231:Carbonic Anhydrase IX / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII
keywords: Acetazolamide; Benzenesulfonamide; Carbonic anhydrase isoforms I, II, IX, XII; Imidazothiadiazoles; Thiazolotriazoles