Benzofuranyl 3,5-bis-polyamine derivatives as time-dependent inhibitors of trypanothione reductase

C. J. Hamilton, A. Saravanamuthu, A. H. Fairlamb, I. M. Eggleston

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Abstract

The synthesis and evaluation of 3,5-disubstituted benzofuran derivatives as time-dependent inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the bis-4-methyl-piperazin-1-yl-propylacrylamide derivative 4 displayed time-dependent activity. The kinetics of time dependent inactivation of trypanothione reductase by 1 and 4 have been determined and are compared and discussed herein. (C) 2003 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)3683-3693
Number of pages11
JournalBioorganic & Medicinal Chemistry
Volume11
Issue number17
DOIs
Publication statusPublished - 2003

Keywords

  • ERYTHROCYTES
  • OXIDATIVE STRESS
  • GLUTATHIONE-REDUCTASE

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