A newly described -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 (k(cat) of 6.7 x 10(5) s(-1) and a k(cat)/K-m of 8.9 x 10(7) M-1 s(-1)). A panel of sulfonamides 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 (K(I)s 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 (K(I)s of 509-845 nM) compared to other sulfonamides investigated here. As -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.

Sulfonamide Inhibition Studies of a New β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica / Bua, Silvia; Haapanen, Susanna; Kuuslahti, Marianne; Parkkila, Seppo; Supuran, Claudiu T. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 19:(2018), pp. 0-0. [10.3390/ijms19123946]

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

Bua, Silvia;Supuran, Claudiu T
2018

Abstract

A newly described -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 (k(cat) of 6.7 x 10(5) s(-1) and a k(cat)/K-m of 8.9 x 10(7) M-1 s(-1)). A panel of sulfonamides 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 (K(I)s 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 (K(I)s of 509-845 nM) compared to other sulfonamides investigated here. As -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.
2018
19
0
0
Bua, Silvia; Haapanen, Susanna; Kuuslahti, Marianne; Parkkila, Seppo; Supuran, Claudiu T
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1307864
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