The anticonvulsant sulfamide JNJ-26990990 and its S, S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies
The anticonvulsant sulfamide JNJ-26990990 and its S, S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies(324 views) Di Fiore A, De Simone G, Alterio V, Riccio V, Winum JY, Carta F, Supuran CT
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy. gdesimon@unina.it claudiu.supuran@unifi.it.
Institut des Biomolecules Max Mousseron (IBMM) UMR 5247 CNRS, ENSCM, Universite de Montpellier, Batiment de Recherche Max Mousseron, Ecole Nationale Superieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Universita degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
References: Not available.
The anticonvulsant sulfamide JNJ-26990990 and its S, S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies
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.
The anticonvulsant sulfamide JNJ-26990990 and its S, S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies
The anticonvulsant sulfamide JNJ-26990990 and its S, S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies