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Updated: Mar 26, 2026
Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
Published on: May 31, 2024
Sulfonamide inhibition studies of the β-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae
Sonia Del Prete1, Daniela Vullo2, Viviana De Luca3
1Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy; Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
Insights
Researchers identified potent inhibitors for Vibrio cholerae carbonic anhydrase beta (VchCAβ), a key enzyme in the pathogen. These findings could lead to new drugs targeting this bacterium.
Area of Science:
- Biochemistry
- Microbiology
- Pharmacology
Background:
- Vibrio cholerae, a pathogenic bacterium, possesses three carbonic anhydrases (CAs).
- The alpha-class CA (VchCA) has been previously studied.
- The beta-class CA (VchCAβ) has been recently characterized, including its kinetic properties and crystal structure.
Purpose of the Study:
- To investigate the inhibition of the VchCAβ enzyme using sulfonamides and a sulfamate.
- To identify potential pharmacological tools for studying VchCA and VchCAβ.
- To explore selective inhibitors of VchCAβ over human carbonic anhydrase isoforms.
Main Methods:
- Enzyme inhibition assays were performed using various sulfonamide and sulfamate compounds.
- Inhibition constants (KIs) were determined for each compound against VchCAβ.
- Comparison of inhibitory potencies was made with known carbonic anhydrase inhibitors.
Main Results:
- Deacetylated acetazolamide, methazolamide, and hydrochlorothiazide demonstrated high potency against VchCAβ, with inhibition constants in the nanomolar range (68.2–87.0 nM).
- Sulfanilamide, metanilamide, sulthiame, and saccharin showed medium potency (275–463 nM).
- Clinically used carbonic anhydrase inhibitors like acetazolamide and dorzolamide were found to be micromolar inhibitors (4.51–8.57 μM).
Conclusions:
- Several compounds, particularly deacetylated acetazolamide, methazolamide, and hydrochlorothiazide, are potent inhibitors of VchCAβ.
- The identification of potent and potentially selective inhibitors may facilitate the development of pharmacological tools.
- Further research could elucidate the physiological roles of VchCA and VchCAβ in Vibrio cholerae.
Abstract:
The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β- and γ-classes. VchCA, the α-CA from this species was investigated earlier, whereas the β-class enzyme, VchCAβ was recently cloned, characterized kinetically and its X-ray crystal structure reported by this group. Here we report an inhibition study with sulfonamides and one sulfamate of this enzyme. The best VchCAβ inhibitors were deacetylated acetazolamide and methazolamide and hydrochlorothiazide, which showed inhibition constants of 68.2-87.0nM. Other compounds, with medium potency against VchCAβ, (KIs in the range of 275-463nM), were sulfanilamide, metanilamide, sulthiame and saccharin whereas the clinically used agents such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, zonisamide and celecoxib were micromolar inhibitors (KIs in the range of 4.51-8.57μM). Identification of potent and possibly selective inhibitors of VchCA and VchCAβ over the human CA isoforms, may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzymes.
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