Diversely N-substituted benzenesulfonamides dissimilarly bind to human carbonic anhydrases: crystallographic investigations of N-nitrosulfonamides

Carbonic anhydrases (CAs) are a zinc metalloenzymes that catalyse the reversible hydration of carbon dioxide to bicarbonate and proton, pivotal for a wide range of biological processes. CAs are involved in numerous pathologies and thus represent valuable drug targets in the treatments of several dis...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2178430-2178430
Main Authors: Angeli, Andrea, Ferraroni, Marta, Bonardi, Alessandro, Supuran, Claudiu T., Nocentini, Alessio
Format: Article
Language:English
Subjects:
Benzenesulfonamides
Binding Sites
Carbon dioxide
Carbonic anhydrase
Carbonic Anhydrase Inhibitors - chemistry
Carbonic Anhydrase Inhibitors - pharmacology
Carbonic anhydrases
Carbonic Anhydrases - metabolism
Crystallography
Drug development
Enzymes
Glaucoma
Humans
Hydration
inhibitor
Ischemia
Ligands
metalloenzymes
N-nitrosulfonamides
Neuralgia
Research Paper
Structure-Activity Relationship
Sulfonamides
Sulfonamides - chemistry
Sulfonamides - pharmacology
Therapeutic targets
X-ray crystallography
Zinc
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Summary:Carbonic anhydrases (CAs) are a zinc metalloenzymes that catalyse the reversible hydration of carbon dioxide to bicarbonate and proton, pivotal for a wide range of biological processes. CAs are involved in numerous pathologies and thus represent valuable drug targets in the treatments of several diseases such as glaucoma, obesity, tumour, neuropathic pain, cerebral ischaemia, or as antiinfectives. In the last two decades, several efforts have been made to achieve selective CA inhibitors (CAIs) employing different drug design approaches. However, N-substitutions on primary sulphonamide groups still remain poorly investigated. Here, we reported for the first time the co-crystallisation of a N-nitro sulphonamide derivative with human (h) CA II pointing out the binding site and mode of inhibition of this class of CAIs. The thorough comprehension of the ligand/target interaction might be valuable for a further CAI optimisation for achieving new potent and selective derivatives.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2023.2178430