European Journal of Medicinal Chemistry Reports (Aug 2024)

Stereochemistry matters: Inhibition of carbonic anhydrase II by amino acid derived sulfamates depends on their absolute configuration

  • Toni C. Denner,
  • Elsa L. Klett,
  • Niels V. Heise,
  • René Csuk

Journal volume & issue
Vol. 11
p. 100162

Abstract

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Aminoalcohols were converted into the corresponding enantiomeric phenylsulfonamide sulfamates. These compounds proved to be inhibitors of carbonic anhydrase II. Interestingly, a sulfamate derived from (S)-tryptophan was no inhibitor at all while its (R) configurated enantiomer was an excellent inhibitor of carbonic anhydrase II (CA II). A rationale can be deduced from molecular modeling studies. The sulfamates derived from (R) or (S) proline held very low inhibition constants for this enzyme as Ki = 0.77 μM and 0.70 μM, respectively.

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