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Sulfonamide Inhibition Studies of a New β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica
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 CO(2) hydration reaction (k(cat) of 6.7 × 10(5) s(−1) and a k(cat)/K(m) of 8.9 × 10(7) M(−1) s(−1))....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321117/ https://www.ncbi.nlm.nih.gov/pubmed/30544802 http://dx.doi.org/10.3390/ijms19123946 |
Sumario: | 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 CO(2) hydration reaction (k(cat) of 6.7 × 10(5) s(−1) and a k(cat)/K(m) of 8.9 × 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 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. |
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