title: Isoform-selective inhibitory profile of 2-imidazoline-substituted benzene sulfonamides against a panel of human carbonic anhydrases.
abstract: A series of novel benzene sulfonamides (previously evaluated as selective cyclooxygenase-2 inhibitors) has been profiled against human carbonic anhydrases I, II, IV and VII in an attempt to observe the manifestation of the well established "tail" approach for designing potent, isoform-selective inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1). The compounds displayed an excellent (pKi 7-8) inhibitory profile against CA II (a cytosolic anti-glaucoma and anti-edema biological target) and CA VII (also a cytosolic target believed to be involved in epilepsy and neuropathic pain) and a marked (1-2 orders of magnitude) selectivity against cytosolic isoform CA I and membrane-bound isoform CA IV. The separation of the CA II and CA IV (both of which are catalytically active isoforms, highly sensitive to sulfonamide-type inhibitors) is particularly remarkable and is adding significantly to the global body of data on the chemical biology of carbonic anhydrases.
authors.affiliation: a Neurofarba Department, Universita Degli Studi Di Firenze , Florence , Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: b The Ushinsky Yaroslavl State Pedagogical University , Yaroslavl , Russian Federation.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kalinin
authors.affiliation: a Neurofarba Department, Universita Degli Studi Di Firenze , Florence , Italy.
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanç
authors.affiliation: c Eskitis Institute for Drug Discovery, Griffith University , Brisbane , Queensland , Australia , and.
authors.forename: Pakornwit
authors.initials: P
authors.lastname: Sarnpitak
authors.affiliation: c Eskitis Institute for Drug Discovery, Griffith University , Brisbane , Queensland , Australia , and.
authors.forename: Prashant
authors.initials: P
authors.lastname: Mujumdar
authors.affiliation: c Eskitis Institute for Drug Discovery, Griffith University , Brisbane , Queensland , Australia , and.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Poulsen
authors.affiliation: d Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University , Saint Petersburg , Russian Federation.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Krasavin
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D007093:Imidazoles; D020033:Protein Isoforms; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C017424:2-imidazoline
keywords: 2-imidazolines; Carbonic anhydrases; cyclooxygenase-2 inhibitors; dual active site architecture; isoform selectivity; lipophilic appendages; tail approach