4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases

Kęstutis Rutkauskas; Asta Zubrienė; Ingrida Tumosienė; Kristina Kantminienė; Marytė Kažemėkaitė; Alexey Smirnov; Justina Kazokaitė; Vaida Morkūnaitė; Edita Čapkauskaitė; Elena Manakova; Saulius Gražulis; Zigmuntas J. Beresnevičius; Daumantas Matulis

doi:10.3390/molecules191117356

Molecules (Oct 2014)

4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases

Kęstutis Rutkauskas,
Asta Zubrienė,
Ingrida Tumosienė,
Kristina Kantminienė,
Marytė Kažemėkaitė,
Alexey Smirnov,
Justina Kazokaitė,
Vaida Morkūnaitė,
Edita Čapkauskaitė,
Elena Manakova,
Saulius Gražulis,
Zigmuntas J. Beresnevičius,
Daumantas Matulis

Affiliations

Kęstutis Rutkauskas: Department of Organic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania
Asta Zubrienė: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania
Ingrida Tumosienė: Department of Organic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania
Kristina Kantminienė: Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania
Marytė Kažemėkaitė: Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius LT-08862, Lithuania
Alexey Smirnov: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania
Justina Kazokaitė: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania
Vaida Morkūnaitė: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania
Edita Čapkauskaitė: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania
Elena Manakova: Department of Protein-DNA Interactions, Vilnius University Institute of Biotechnology, Graičiūno 8, Vilnius LT-02241, Lithuania
Saulius Gražulis: Department of Protein-DNA Interactions, Vilnius University Institute of Biotechnology, Graičiūno 8, Vilnius LT-02241, Lithuania
Zigmuntas J. Beresnevičius: Department of Organic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania
Daumantas Matulis: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania

DOI: https://doi.org/10.3390/molecules191117356
Journal volume & issue: Vol. 19, no. 11
pp. 17356 – 17380

Abstract

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A series of N-aryl-β-alanine derivatives and diazobenzenesulfonamides containing aliphatic rings were designed, synthesized, and their binding to carbonic anhydrases (CA) I, II, VI, VII, XII, and XIII was studied by the fluorescent thermal shift assay and isothermal titration calorimetry. The results showed that 4-substituted diazobenzenesulfonamides were more potent CA binders than N-aryl-β-alanine derivatives. Most of the N-aryl-β-alanine derivatives showed better affinity for CA II while diazobenzenesulfonamides possessed nanomolar affinities towards CA I isozyme. X-ray crystallographic structures showed the modes of binding of both compound groups.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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