Download MendeleyThe anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.
Di Fiore, A., De Simone, G., Alterio, V., Riccio, V., Winum, J.Y., Carta, F., Supuran, C.T.(2016) Org Biomol Chem 14: 4853-4858
- PubMed: 27151329
- DOI: https://doi.org/10.1039/c6ob00803h
- Primary Citation of Related Structures:
5FDC, 5FDI - PubMed 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.
Organizational Affiliation:
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy. [email protected] [email protected].
