title: Synthesis of novel acridine and bis acridine sulfonamides with effective inhibitory activity against the cytosolic carbonic anhydrase isoforms II and VII.
abstract: 4-Amino-N-(4-sulfamoylphenyl)benzamide was synthesized by reduction of 4-nitro-N-(4-sulfamoylphenyl)benzamide and used to synthesize novel acridine sulfonamide compounds, by a coupling reaction with cyclic-1,3-diketones and aromatic aldehydes. The new compounds were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely the cytosolic isoforms hCA I, II and VII. hCA I was inhibited in the micromolar range by the new compounds (KIs of 0.16-9.64 μM) whereas hCA II and VII showed higher affinity for these compounds, with KIs in the range of 15-96 nM for hCA II, and of 4-498 nM for hCA VII. The structure-activity relationships for the inhibition of these isoforms with the acridine-sulfonamides reported here were also elucidated.
authors.affiliation: Chemistry Department, Faculty of Arts and Science, Dumlupınar University, Kütahya, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Ulus
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yeşildağ
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanç
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
authors.forename: Muharrem
authors.initials: M
authors.lastname: Kaya
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000166:Acridines / Q000737:chemistry*; 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; D007700:Kinetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000166:Acridines; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013449:Sulfonamides; C484811:bis-acridine; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI
keywords: Acridine; Carbonic anhydrase; Enzyme inhibition; Isoforms CA I, II and VII; Sulfonamide