Planta Med 2000; 66(2): 106-109
DOI: 10.1055/s-2000-11123
Original Paper
Georg Thieme Verlag Stuttgart · New York

Glutathione Adducts of Helenalin and 11α,13-Dihydrohelenalin Acetate Inhibit Glutathione S-Transferase from Horse Liver1

Thomas  J. Schmidt2
  • 1 Part 6 in the series “Helenanolide Type Sesquiterpene Lactones”. For part 5 see Ref. [2]
  • 2 Institut für Pharmazeutische Biologie der Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Abstract

The 2-mono- and 2,13-bis-glutathionyl adducts of helenalin and the 2-monoglutathionyl adduct of 11α,13-dihydrohelenalin acetate were previously shown to be formed by spontaneous Michael addition at physiological pH. In living cells, glutathione (GSH) conjugation of many types of electrophilic agents is catalysed by a family of GSH S-transferase enzymes (GST). The capability of a glutathione S-transferase from horse liver to catalyze the reaction of helenalin and other helenanolides with GSH was investigated. The enzyme did not accelerate GSH conjugation of helenalin, 11α,13-dihydrohelenalin, or 2-deacetyl-6-deoxychamissonolide. The GSH-adducts, formed by spontaneous reaction, were found to be inhibitors of this enzyme. Free helenalin, a potent inhibitor of many enzymes containing free sulfhydryl groups, did not show any inhibitory activity on GST. It was thus demonstrated that GSH-adducts of sesquiterpene lactones possess their own specific biological activity. Two further enzymes using GSH as substrate, glutathione reductase and glyoxalase I, were not influenced by free helenalin or its GSH-adducts.

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Dr. Thomas J. Schmidt

Institut für Pharmazeutische Biologie

der Heinrich-Heine-Universität Düsseldorf

Universitätsstraße 1, Geb. 26 23

40225 Düsseldorf

Germany

Email: schmidtt@uni-duesseldorf.de

Phone: +49-211-811-1923

Fax: +49-211-811-4179

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