Schmidt T J
Institut für Pharmazeutische Biologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Planta Med. 2000 Mar;66(2):106-9. doi: 10.1055/s-2000-11123.
The 2-mono- and 2,13-bis-glutathionyl adducts of helenalin and the 2-monoglutathionyl adduct of 11 alpha,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, 11 alpha,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.
海伦内酯的2-单谷胱甘肽加合物和2,13-双谷胱甘肽加合物以及11α,13-二氢海伦内酯乙酸酯的2-单谷胱甘肽加合物先前已证明是在生理pH值下通过自发迈克尔加成形成的。在活细胞中，许多亲电试剂的谷胱甘肽（GSH）共轭反应是由谷胱甘肽S-转移酶（GST）家族催化的。研究了马肝中的一种谷胱甘肽S-转移酶催化海伦内酯和其他海勒烷型内酯与GSH反应的能力。该酶并未加速海伦内酯、11α,13-二氢海伦内酯或2-脱乙酰基-6-脱氧沙米松内酯的GSH共轭反应。发现通过自发反应形成的GSH加合物是该酶的抑制剂。游离的海伦内酯是许多含游离巯基酶的有效抑制剂，但对GST没有任何抑制活性。因此证明倍半萜内酯的GSH加合物具有其自身特定的生物活性。另外两种以GSH为底物的酶，谷胱甘肽还原酶和乙二醛酶I，不受游离海伦内酯或其GSH加合物的影响。
