title: Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV.
abstract: Aromatic amides comprising branched aliphatic carboxylic acids and 4-aminobenzenesulfonamide were evaluated for their inhibition of carbonic anhydrase (CA) isoforms. Of the most anticonvulsant-active compounds (2, 4, 13, 16, and 17), only 13, 16, and 17 were potent inhibitors of CAs VII and XIV. Compounds 9, 14, and 19 inhibited CA II, while 10 and 12 inhibited all isoforms. Structural studies suggest that differences in the active sites' hydrophobicity modulate the affinity of the inhibitors.
authors.affiliation: Institute for Drug Research, The Hebrew University of Jerusalem , Jerusalem, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Hen
authors.forename: Meir
authors.initials: M
authors.lastname: Bialer
authors.forename: Boris
authors.initials: B
authors.lastname: Yagen
authors.forename: Alfonso
authors.initials: A
authors.lastname: Maresca
authors.forename: Mayank
authors.initials: M
authors.lastname: Aggarwal
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Robbins
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D018360:Crystallography, X-Ray; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020033:Protein Isoforms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013449:Sulfonamides; D002256:Carbonic Anhydrases