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

Autor: Seppo Parkkila, Marianne Kuuslahti, Susanna Haapanen, Silvia Bua, Claudiu T. Supuran
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
carbonic anhydrase
01 natural sciences
Article
Catalysis
Inorganic Chemistry
lcsh:Chemistry
Structure-Activity Relationship
03 medical and health sciences
Entamoeba histolytica
Carbonic anhydrase
sulfonamides
medicine
Humans
Amino Acid Sequence
Enzyme kinetics
Physical and Theoretical Chemistry
Carbonic Anhydrase Inhibitors
Methazolamide
sulfamates
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Carbonic Anhydrases
metalloenzymes
Ethoxzolamide
biology
Chemistry
protozoan
Organic Chemistry
Sulfonamide (medicine)
Dichlorophenamide
General Medicine
biology.organism_classification
0104 chemical sciences
Computer Science Applications
inhibitor
Kinetics
010404 medicinal & biomolecular chemistry
030104 developmental biology
Biochemistry
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Acetazolamide
medicine.drug
Zdroj: International Journal of Molecular Sciences
Volume 19
Issue 12
International Journal of Molecular Sciences, Vol 19, Iss 12, p 3946 (2018)
ISSN: 1422-0067
DOI: 10.3390/ijms19123946
Popis: A newly described &beta
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&minus
1 and a kcat/Km of 8.9 ×
107 M&minus
1 s&minus
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&ndash
89 nM), whereas some sulfanilyl-sulfonamides showed activities in the range of 285&ndash
331 nM. Acetazolamide, methazolamide, ethoxzolamide, and dichlorophenamide were less effective inhibitors (KIs of 509&ndash
845 nM) compared to other sulfonamides investigated here. As &beta
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.
Databáze: OpenAIRE
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