Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulphamates.

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Ho YT, Purohit A, Vicker N, Newman SP, Robinson JJ, Leese MP, Ganeshapillai D, Woo LW, Potter BV, Reed MJ

Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulphamates.

Biochem Biophys Res Commun. 2003 Jun 13;305(4):909-14.

PubMed ID
12767917 [ View in PubMed
]
Abstract

Carbonic anhydrases (CAs) are expressed by many solid tumours where they may act to confer a growth advantage on malignant tissues. In this study we have examined the ability of a series of steroidal and non-steroidal sulphamates (originally developed as steroid sulphatase inhibitors) and related compounds to inhibit human CAII (hCAII) activity in vitro. Using a 96-well plate assay, oestrone-3-O-sulphamate (EMATE) and two coumarin-based sulphamate drugs (667 COUMATE and STX 118) were found to have IC(50) values of 25-59 nM for the inhibition of hCAII activity. These compounds therefore have a similar CAII inhibitory potency to that of acetazolamide (IC(50)=25 nM), a known hCAII inhibitor. Docking studies have been performed with selected compounds to the crystal structure of hCAII and excellent correlation of scores with biological activity was observed. This agrees with our recent observations when we were the first to report the inhibition of hCAII by STS inhibitors. These studies and initial results with docking to the crystal structure of the extracellular domain of hCAXII indicate that the STS sulphamate ester inhibitors should also be interesting candidates to pursue as inhibitors of CA isozymes that are over-expressed in human tumours.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 2IC 50 (nM)257.820Details
IrosustatCarbonic anhydrase 2IC 50 (nM)257.820Details