Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV.

Article Details

Citation

Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran CT

Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV.

J Med Chem. 2011 Jun 9;54(11):3977-81. doi: 10.1021/jm200209n. Epub 2011 May 9.

PubMed ID
21506569 [ View in PubMed
]
Abstract

Aromatic amides comprising branched aliphatic carboxylic acids and 4-aminobenzenesulfonamide were evaluated for their inhibition of carbonic anhydrase (CA) isoforms. Of the most anticonvulsant-active compounds (2, 4, 13, 16, and 17), only 13, 16, and 17 were potent inhibitors of CAs VII and XIV. Compounds 9, 14, and 19 inhibited CA II, while 10 and 12 inhibited all isoforms. Structural studies suggest that differences in the active sites' hydrophobicity modulate the affinity of the inhibitors.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 14Ki (nM)41N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
AcetazolamideCarbonic anhydrase 7Ki (nM)2.5N/AN/ADetails
TopiramateCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)10N/AN/ADetails
ZonisamideCarbonic anhydrase 1Ki (nM)56N/AN/ADetails
ZonisamideCarbonic anhydrase 14Ki (nM)5250N/AN/ADetails
ZonisamideCarbonic anhydrase 2Ki (nM)35N/AN/ADetails
ZonisamideCarbonic anhydrase 7Ki (nM)117N/AN/ADetails