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BioMed Research International
Volume 2014, Article ID 638902, 9 pages
http://dx.doi.org/10.1155/2014/638902
Research Article

Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII

1Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania
2Department of Bioinformatics, Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania
3Department of Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia

Received 28 February 2014; Revised 28 April 2014; Accepted 28 May 2014; Published 3 September 2014

Academic Editor: Vincenzo Alterio

Copyright © 2014 Vaida Morkūnaitė et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.