Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.

Article Details

Citation
Copy to clipboard

Temperini C, Cecchi A, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2567-73. doi: 10.1016/j.bmcl.2008.03.051. Epub 2008 Mar 20.

PubMed ID
18374572 [ View in PubMed
]
Abstract

Diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide, and bumetanide containing primary sulfamoyl moieties were reevaluated as inhibitors of 12 human carbonic anhydrases (hCAs, EC 4.2.1.1). These drugs considerably inhibit (low nanomolar range) some CA isozymes involved in critical physiologic processes, among the 16 present in vertebrates, for example, metolazone against CA VII, XII, and XIII, chlorthalidone against CA VB, VII, IX, XII, and XIII, indapamide against CA VII, IX, XII, and XIII, furosemide against CA I, II, and XIV, and bumetanide against CA IX and XII. The X-ray crystal structure of the hCA II-indapamide adduct was also resolved at high resolution.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
QuinethazoneCarbonic anhydrase 1ProteinHumans
Yes
Inhibitor
Details
QuinethazoneCarbonic anhydrase 2ProteinHumans
Yes
Inhibitor
Details
Polypeptides
NameUniProt ID
Carbonic anhydrase 2P00918Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 3Ki (nM)2000007.425Details
DiclofenamideCarbonic anhydrase 3Ki (nM)>2000007.425Details
EthoxzolamideCarbonic anhydrase 3Ki (nM)>2000007.425Details
FurosemideCarbonic anhydrase 2Ki (nM)657.425Details
HydroflumethiazideCarbonic anhydrase 1Ki (nM)28407.425Details
HydroflumethiazideCarbonic anhydrase 12Ki (nM)3057.425Details
HydroflumethiazideCarbonic anhydrase 2Ki (nM)4357.425Details
HydroflumethiazideCarbonic anhydrase 4Ki (nM)47807.425Details
HydroflumethiazideCarbonic anhydrase 9Ki (nM)4127.425Details
MethazolamideCarbonic anhydrase 3Ki (nM)>2000007.425Details
QuinethazoneCarbonic anhydrase 1Ki (nM)350007.425Details
QuinethazoneCarbonic anhydrase 2Ki (nM)12607.425Details