title: Saccharin sulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.
abstract: A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs weakly, exhibiting the affinities of 1-10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1-10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Vaida
authors.initials: V
authors.lastname: Morkūnaitė
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Lina
authors.initials: L
authors.lastname: Baranauskienė
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Asta
authors.initials: A
authors.lastname: Zubrienė
authors.affiliation: Department of Bioinformatics, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Visvaldas
authors.identifier: 0000-0002-5427-0175
authors.initials: V
authors.lastname: Kairys
authors.affiliation: Department of Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Jekaterina
authors.identifier: 0000-0001-8845-0193
authors.initials: J
authors.lastname: Ivanova
authors.affiliation: Department of Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Pēteris
authors.initials: P
authors.lastname: Trapencieris
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Daumantas
authors.identifier: 0000-0002-6178-6276
authors.initials: D
authors.lastname: Matulis
mesh_terms: D002151:Calorimetry; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D062105:Molecular Docking Simulation; D011994:Recombinant Proteins / Q000378:metabolism; D012439:Saccharin / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; D013449:Sulfonamides; D002256:Carbonic Anhydrases; D012439:Saccharin