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Int. J. Mol. Sci. 2018, 19(12), 3946; https://doi.org/10.3390/ijms19123946

Sulfonamide Inhibition Studies of a New β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica

1
Sezione di Scienze Farmaceutiche e Nutraceutiche, Neurofarba Dept., Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy
2
Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland
3
Fimlab Ltd., Tampere University Hospital, 33100 Tampere, Finland
*
Author to whom correspondence should be addressed.
Received: 9 November 2018 / Revised: 27 November 2018 / Accepted: 6 December 2018 / Published: 8 December 2018
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Abstract

A newly described β-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan Entamoeba histolytica, EhiCA, was recently shown to possess a significant catalytic activity for the physiologic CO2 hydration reaction (kcat of 6.7 × 105 s−1 and a kcat/Km of 8.9 × 107 M−1 s−1). A panel of sulphonamides and one sulfamate, some of which are clinically used drugs, were investigated for their inhibitory properties against EhiCA. The best inhibitors detected in the study were 4-hydroxymethyl/ethyl-benzenesulfonamide (KIs of 36–89 nM), whereas some sulfanilyl-sulfonamides showed activities in the range of 285–331 nM. Acetazolamide, methazolamide, ethoxzolamide, and dichlorophenamide were less effective inhibitors (KIs of 509–845 nM) compared to other sulfonamides investigated here. As β-CAs are not present in vertebrates, the present study may be useful for detecting lead compounds for the design of more effective inhibitors with potential to develop anti-infectives with alternative mechanisms of action. View Full-Text
Keywords: carbonic anhydrase; metalloenzymes; protozoan; Entamoeba histolytica; sulfonamides; sulfamates; inhibitor carbonic anhydrase; metalloenzymes; protozoan; Entamoeba histolytica; sulfonamides; sulfamates; inhibitor
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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 (CC BY 4.0).
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Bua, S.; Haapanen, S.; Kuuslahti, M.; Parkkila, S.; Supuran, C.T. Sulfonamide Inhibition Studies of a New β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica. Int. J. Mol. Sci. 2018, 19, 3946.

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