3b4f
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Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies
OverviewOverview
2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its, interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the, search of compounds with good inhibitory activity against isozymes with, medicinal chemistry applications, such as CA I, II, VA, VB, VII, IX, and, XII among others. This sulfonamide is a potent inhibitor of CA I and II, (K(I)s of 7.2-7.5 nM), a medium potency inhibitor of CA VII, IX, XII, and, XIV, and a weak inhibitor against the other ubiquitous isoforms, making it, thus a very interesting clinical candidate for situations in which a, strong inhibition of CA I and II is needed. The crystal structure of the, hCA II adduct of this sulfonamide revealed many favorable interactions, between the inhibitor and the enzyme which explain its strong low, nanomolar affinity for this isoform but may also be exploited for the, design of effective inhibitors incorporating bicyclic moieties.
About this StructureAbout this Structure
3B4F is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
ReferenceReference
Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies., Guzel O, Temperini C, Innocenti A, Scozzafava A, Salman A, Supuran CT, Bioorg Med Chem Lett. 2008 Jan 1;18(1):152-8. Epub 2007 Nov 4. PMID:18024029
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