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

Y. T. Ho, A. Purohit, N. Vicker, S. P. Newman, J. J. Robinson, M. P. Leese, D. Ganeshapillai, L. W. L. Woo, B. V. L Potter, M. J. Reed

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Carbonic anhydrases (CAs) are expressed by many solid tumours where they may act to confer a growth advantage on malignant tissues. 111 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 IC50 values of 25-59nM for the inhibition of hCAII activity. These compounds therefore have a similar CAII inhibitory potency to that of acetazolamide (IC50=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. (C) 2003 Elsevier Science (USA). All rights reserved.
Original languageEnglish
Pages (from-to)909-914
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number4
DOIs
Publication statusPublished - 2003

Fingerprint Dive into the research topics of 'Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulphamates'. Together they form a unique fingerprint.

  • Cite this

    Ho, Y. T., Purohit, A., Vicker, N., Newman, S. P., Robinson, J. J., Leese, M. P., Ganeshapillai, D., Woo, L. W. L., Potter, B. V. L., & Reed, M. J. (2003). Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulphamates. Biochemical and Biophysical Research Communications, 305(4), 909-914. https://doi.org/10.1016/s0006-291x(03)00865-9