BIOMAT Database Logo BIOMAT Database Logo

Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic anhydrases. 2018

Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Saulėtekio al. 7, Vilnius LT-10257, Lithuania.

Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D002256 Carbonic Anhydrases A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1. Carbonate Dehydratase,Carbonic Anhydrase,Anhydrases, Carbonic,Dehydratase, Carbonate
D002257 Carbonic Anhydrase Inhibitors A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000096926 Benzenesulfonamides A group of compounds that contain sulfonamide group S-linked to a benzene ring. Many benzenesulfonamide derivatives are pharmaceuticals (e.g., BOSENTAN; SULFAPYRIDINE; and SULFADIAZINE; CELECOXIB) as their sulfonamide moiety target various enzymes (e.g., CARBONIC ANHYDRASES; ACETYLCHOLINESTERASE; BUTYRYLCHOLINESTERASE; and CYCLOOXYNENASE 2). Benzenesulfonamide,Benzenesulfonamide Derivatives,Benzenesulfonamide Monosodium Salt,Benzenesulphonamides,Benzosulfonamides
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole

Related Publications

Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases.
April 2022, Pharmaceuticals (Basel, Switzerland),
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Inhibition of β-carbonic anhydrases with ureido-substituted benzenesulfonamides.
January 2011, Bioorganic & medicinal chemistry letters,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Pyrrolidinone-bearing methylated and halogenated benzenesulfonamides as inhibitors of carbonic anhydrases.
January 2019, Bioorganic & medicinal chemistry,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Pyridazinone substituted benzenesulfonamides as potent carbonic anhydrase inhibitors.
February 2016, Bioorganic & medicinal chemistry letters,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Indapamide-like benzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, and XIII.
November 2010, Bioorganic & medicinal chemistry,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Diversely N-substituted benzenesulfonamides dissimilarly bind to human carbonic anhydrases: crystallographic investigations of N-nitrosulfonamides.
December 2023, Journal of enzyme inhibition and medicinal chemistry,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Benzenesulfonamides Incorporating Hydantoin Moieties Effectively Inhibit Eukaryoticand Human Carbonic Anhydrases.
November 2022, International journal of molecular sciences,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Synthesis of benzamide derivatives with thiourea-substituted benzenesulfonamides as carbonic anhydrase inhibitors.
February 2021, Archiv der Pharmazie,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms.
January 2020, European journal of medicinal chemistry,
Edita Čapkauskaitė, and Asta Zubrienė, and Vaida Paketurytė, and David D Timm, and Sigitas Tumkevičius, and Daumantas Matulis
4-Cyanamido-substituted benzenesulfonamides act as dual carbonic anhydrase and cathepsin inhibitors.
October 2023, Bioorganic chemistry,
Copied contents to your clipboard!