Frölich Sonja, Schubert Carola, Bienzle Ulrich, Jenett-Siems Kristina
Institut für Pharmazie (Pharmazeutische Biologie), Freie Universität Berlin, Königin-Luise-Str. 2-4, D-14195 Berlin, Germany.
J Antimicrob Chemother. 2005 Jun;55(6):883-7. doi: 10.1093/jac/dki099. Epub 2005 Apr 11.
There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. Chalcones are one of the classes of natural products that are known to possess antiplasmodial properties. Therefore, the in vitro antiplasmodial activity of the main hop chalcone xanthohumol and seven derivatives was evaluated. In addition, the influence of the compounds on glutathione (GSH)-dependent haemin degradation was analysed to determine its contribution to the antimalarial effect of chalcones.
In vitro antiplasmodial activity was evaluated against the chloroquine-sensitive strain poW and the multiresistant clone Dd2 using a [(3)H]hypoxanthine-incorporation assay. Inhibition of GSH-dependent haemin degradation was analysed by a multiwell plate assay at 11 microM.
Of the eight compounds tested, four possessed activity with IC(50) values<25 microM against at least one of the two strains of Plasmodium falciparum. The main hop chalcone, xanthohumol, was most active with IC(50) values of 8.2+/-0.3 (poW) and 24.0 +/- 0.8 microM (Dd2). Three of these compounds were additionally active in the haemin-degradation assay.
The results demonstrate for the first time the ability of chalcone derivatives to interfere with the haemin-degradation process of P. falciparum. This effect might contribute to their antiplasmodial activity. Nevertheless, as one compound showed inhibition of P. falciparum without being able to interact with GSH-dependent haemin degradation, other modes of action must add to the observed antiparasitic activity of hop chalcones.
由于氯喹耐药性的传播以及可用药物数量有限，迫切需要发现新的抗疟药物。查耳酮是一类已知具有抗疟原虫特性的天然产物。因此，评估了主要啤酒花查耳酮黄腐酚及其七种衍生物的体外抗疟原虫活性。此外，分析了这些化合物对谷胱甘肽（GSH）依赖性血红素降解的影响，以确定其对查耳酮抗疟作用的贡献。
使用[（3）H]次黄嘌呤掺入试验，针对氯喹敏感株poW和多耐药克隆Dd2评估体外抗疟原虫活性。通过在11 microM下的多孔板试验分析对GSH依赖性血红素降解的抑制作用。
在所测试的八种化合物中，有四种对至少两种恶性疟原虫菌株中的一种具有活性，IC（50）值<25 microM。主要啤酒花查耳酮黄腐酚活性最高，IC（50）值分别为8.2±0.3（poW）和24.0±0.8 microM（Dd2）。其中三种化合物在血红素降解试验中也具有活性。
结果首次证明查耳酮衍生物能够干扰恶性疟原虫的血红素降解过程。这种作用可能有助于其抗疟原虫活性。然而，由于一种化合物显示出对恶性疟原虫的抑制作用，但无法与GSH依赖性血红素降解相互作用，其他作用方式必定对观察到的啤酒花查耳酮的抗寄生虫活性有所贡献。
