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Issue 21, 2016
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The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies

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Abstract

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.

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

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Publication details

The article was received on 14 Apr 2016, accepted on 27 Apr 2016 and first published on 28 Apr 2016


Article type: Paper
DOI: 10.1039/C6OB00803H
Org. Biomol. Chem., 2016,14, 4853-4858

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

    A. Di Fiore, G. De Simone, V. Alterio, V. Riccio, J. Winum, F. Carta and C. T. Supuran, Org. Biomol. Chem., 2016, 14, 4853
    DOI: 10.1039/C6OB00803H

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