title: Carbonic anhydrase inhibitors: Synthesis and inhibition of the cytosolic mammalian carbonic anhydrase isoforms I, II and VII with benzene sulfonamides incorporating 4,5,6,7-tetrachlorophthalimide moiety.
abstract: A series of 4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1-8) was synthesized by reaction of benzene sulfonamides incorporating primary amino moieties with 4,5,6,7-tetrachlorophthalic anhydride. These sulfonamides were assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Some of these compounds showed very good in vitro human carbonic anhydrase (hCA) isoforms I, II and VII inhibitory properties, with affinities in the low nanomolar range. Inhibition activities against hCA I were in the range of 159-444nM; against hCA II in the range of 2.4-4515nM, and against hCA VII in the range of 1.3-469nM. The structure-activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoform being established.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, India. kalyansethi@gmail.com
authors.forename: Kalyan K
authors.initials: KK
authors.lastname: Sethi
authors.forename: Saurabh M
authors.initials: SM
authors.lastname: Verma
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanç
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010797:Phthalimides / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D010797:Phthalimides; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C037431:phthalimide; C477051:carbonic anhydrase VI
keywords: 4,5,6,7-Tetrachloro-1,3-dioxoisoindolin-2-yl benzenesulfonamide; Benzenesulfonamide; Human carbonic anhydrase inhibitors; Structure–activity relationship