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PDBsum entry 3b4f
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References listed in PDB file
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Key reference
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Title
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Carbonic anhydrase inhibitors. Interaction of 2-(Hydrazinocarbonyl)-3-Phenyl-1h-Indole-5-Sulfonamide with 12 mammalian isoforms: kinetic and X-Ray crystallographic studies.
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Authors
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O.Güzel,
C.Temperini,
A.Innocenti,
A.Scozzafava,
A.Salman,
C.T.Supuran.
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Ref.
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Bioorg Med Chem Lett, 2008,
18,
152-158.
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PubMed id
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Abstract
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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.
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