title: Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds.
abstract: Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors.
authors.affiliation: Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, Russian Federation. Electronic address: m.krasavin@spbu.ru.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Krasavin
authors.affiliation: The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Korsakov
authors.affiliation: The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Zvonaryova
authors.affiliation: The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation.
authors.forename: Evgenii
authors.initials: E
authors.lastname: Semyonychev
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.affiliation: Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, Russian Federation.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kalinin
authors.affiliation: Neurofarba Dept., Universita degli Studi di Firenze, Florence, Italy.
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanç
authors.affiliation: Neurofarba Dept., Universita degli Studi di Firenze, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054879:Halogenation; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007555:Isoxazoles; D013449:Sulfonamides
keywords: Alternative binding mode; Aromatic sulfochlorination; Carbonic anhydrase inhibitors; Isoform selectivity; Primary sulfonamide; Zinc binding group