The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2016

The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies

Résumé

JNJ-26990990 ((benzo[b]thien-3-yl)methyl)sulfamide, a sulfamide derivative structurally related to the antiepileptic drug zonisamide, was reported to be devoid of carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties. Here we report that JNJ-26990990 and its S,S-dioxide analog significantly inhibit six human (h) isoforms, hCA I, II, VII, IX, XII and XIV, involved in crucial physiological processes. Inhibition and X-ray crystallographic data for the binding of the two compounds to these enzymes show significant similarity with the zonisamide inhibitory pattern. These findings prompted us to reconsider the structural/pharmacological requirements for designing effective antiepileptics possessing zinc-binding groups of the sulfamide, sulfamate or sulfonamide type in their molecules.

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Chimie
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Dates et versions

hal-03621601 , version 1 (28-03-2022)

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Anna Di Fiore, Giuseppina de Simone, Vincenzo Alterio, Vincenzo Riccio, Jean-Yves Winum, et al.. The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies. Organic & Biomolecular Chemistry, 2016, 14 (21), pp.4853-4858. ⟨10.1039/C6OB00803H⟩. ⟨hal-03621601⟩
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