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

Molecules

Kęstutis Rutkauskas⁴  Asta Zubrienė⁵  Ingrida Tumosienė⁴  Kristina Kantminienė³  Marytė Ka៮mėkaitė¹  Alexey Smirnov⁵  Justina Kazokaitė⁵  Vaida Morkūnaitė⁵  Edita ჊pkauskaitė⁵  Elena Manakova²  Saulius Gražulis²  Zigmuntas J. Beresnevičius⁴  Daumantas Matulis⁵ 

[1] Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius LT-08862, Lithuania; E-Mail:;Department of Protein-DNA Interactions, Vilnius University Institute of Biotechnology, Graičiūno 8, Vilnius LT-02241, Lithuania; E-Mails:;Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania; E-Mail:;Department of Organic Chemistry, Kaunas University of Technology, Kaunas LT-50254, Lithuania; E-Mails:;Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania; E-Mails:

关键词: benzenesulfonamide;    hydrazide;    hydrazone;    azole;    triazene;    carbonic anhydrase;    fluorescent thermal shift assay;    ThermoFluor^®;    isothermal titration calorimetry;   

DOI  :  10.3390/molecules191117356

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.