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PDBsum entry 4rux
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References listed in PDB file
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Key reference
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Title
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A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.
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Authors
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F.Carta,
L.Di cesare mannelli,
M.Pinard,
C.Ghelardini,
A.Scozzafava,
R.Mckenna,
C.T.Supuran.
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Ref.
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Bioorg Med Chem Lett, 2015,
23,
1828-1840.
[DOI no: ]
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PubMed id
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Abstract
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A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors
which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with
several derivatives of ethoxzolamide and sulfanilamide are reported. These
derivatives were investigated as inhibitors of the metalloenzyme carbonic
anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear
to be involved in pain. These sulfonamides showed modest inhibition against the
cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII,
IX and XII inhibitors. X-ray crystallographic data for the adduct of several
such sulfonamides with CA II allowed us to rationalize the good inhibition data.
In a mice model of neuropathic pain induced by oxaliplatin, one of the strong CA
II/VII inhibitors reported here induced a long lasting pain relieving effect, a
fact never observed earlier. This is the first report of rationally designed
sulfonamide CA inhibitors with pain effective modulating effects.
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