title: Discovery of Benzenesulfonamides with Potent Human Carbonic Anhydrase Inhibitory and Effective Anticonvulsant Action: Design, Synthesis, and Pharmacological Assessment.
abstract: We report two series of novel benzenesulfonamide derivatives acting as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The synthesized compounds were tested against human (h) isoforms hCA I, hCA II, hCA VII, and hCA XII. The first series of compounds, 4-(3-(2-(4-substitued piperazin-1-yl)ethyl)ureido)benzenesulfonamides, showed low nanomolar inhibitory action against hCA II, being less effective against the other isoforms. The second series, 2-(4-substitued piperazin-1-yl)-N-(4-sulfamoylphenyl)acetamide derivatives, showed low nanomolar inhibitory activity against hCA II and hCA VII, isoforms involved in epileptogenesis. Some of these derivatives were evaluated for their anticonvulsant activity and displayed effective seizure protection against MES and scPTZ induced seizures in Swiss Albino mice. These sulfonamides were also found effective upon oral administration to Wistar rats and inhibited MES induced seizure episodes in this animal model of the disease. Some of the new compounds showed a long duration of action in the performed time course anticonvulsant studies, being nontoxic in subacute toxicity studies.
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi , Delhi, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi , Delhi, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Dipartimento Neurofarba, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche e Nutraceutiche , Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Angeli
authors.affiliation: Istituto di Biostrutture e Bioimmagini (IBB) CNR ,via Mezzocannone, Naples, Italy.
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.affiliation: Istituto di Biostrutture e Bioimmagini (IBB) CNR ,via Mezzocannone, Naples, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Buonanno
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi , Delhi, India.
authors.forename: Manisha
authors.identifier: 0000-0001-8942-0578
authors.initials: M
authors.lastname: Tiwari
authors.affiliation: Dipartimento Neurofarba, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche e Nutraceutiche , Florence, Italy.
authors.forename: Claudiu T
authors.identifier: 0000-0003-4262-0323
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D020033:Protein Isoforms; D013449:Sulfonamides; D000096926:Benzenesulfonamides