title: Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII.
abstract: Four novel scaffolds consisting of total 24 compounds (1a-1o, 2a-2c, 3a-3c and 4a-4c) bearing aromatic sulfonamide and coumarin moieties connected through various linkers were synthesized in order to synergize the inhibition potential of both the moieties against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). All compounds were found to be potent inhibitors of tumor associated hCA IX & XII while at the same time required large amounts to inhibit off-targeted housekeeping hCA I & II. Selectivity was more pronounced against hCA II over I, and hCA XII over IX. Results were compared with antitumor drug acetazolamide. One derivative 2b of series 2 was found to be a better selective inhibitor of hCA IX and XII.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Chandak
authors.affiliation: Università degli Studi di Fierenze, 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: Università degli Studi di Fierenze, 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: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000071231:Carbonic Anhydrase IX / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D007527:Isoenzymes; D013449:Sulfonamides; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Acetazolamide; Coumarin; Human carbonic anhydrase isoforms I, II, IX, XII; Sulfonamide; Synergistic inhibition