Kocken Clemens H M, van der Wel Annemarie, Arbe-Barnes Sarah, Brun Reto, Matile Hugues, Scheurer Christian, Wittlin Sergio, Thomas Alan W
Biomedical Primate Research Centre, Department of Parasitology, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands.
Exp Parasitol. 2006 Jul;113(3):197-200. doi: 10.1016/j.exppara.2005.12.016. Epub 2006 Feb 3.
Plasmodium vivax is an important human pathogen causing malaria in more temperate climates of the world. Similar to Plasmodium falciparum, the causative agent for malaria tropica, drug resistance is beginning to emerge for this parasite species and this hampers adequate treatment of infection. We have used a short-term ex vivo drug assay to monitor activity of OZ277 (RBx-11160), a fully synthetic anti-malarial peroxide, and the diamidine DB75 against P. vivax. For both compounds as well as the anti-malarial reference compounds artesunate, artemether, and chloroquine, the in vitro IC(50) values were determined in one-cycle hypoxanthine incorporation assays. Results from such assays were found to be very similar compared to IC(50) values obtained from one-cycle P. falciparum hypoxanthine assays. We demonstrate the anti-parasite activity of OZ277 and the reference compounds to be faster than that of DB75. These data warrant clinical testing of OZ277 against P. vivax malaria and support recent data on clinical activity against P. vivax for DB75.
间日疟原虫是一种重要的人类病原体，在世界上气候较为温和的地区引发疟疾。与热带疟原虫（疟疾热带型的病原体）疟原虫 falciparum 相似，这种寄生虫物种也开始出现耐药性，这妨碍了对感染的充分治疗。我们使用了一种短期体外药物检测方法来监测 OZ277（RBx - 11160）的活性，OZ277 是一种全合成抗疟过氧化物，以及双脒 DB75 对间日疟原虫的作用。对于这两种化合物以及抗疟参考化合物青蒿琥酯、蒿甲醚和氯喹，在单周期次黄嘌呤掺入试验中测定了体外 IC(50) 值。与从单周期疟原虫 falciparum 次黄嘌呤试验获得的 IC(50) 值相比，此类试验的结果非常相似。我们证明 OZ277 和参考化合物的抗寄生虫活性比 DB75 更快。这些数据为 OZ277 针对间日疟原虫疟疾的临床试验提供了依据，并支持了近期关于 DB75 对间日疟原虫临床活性的数据。
