Quantifying Redox Potentials for Artemisinin Resistant (ARTR) Malaria

“量化青蒿素耐药疟疾的氧化还原电位” 利用最近基于香豆素的荧光GSH探针的表征，我们合成的GSH较少 昂贵和更方便的探针，包括有趣的吗啉衍生物和葡聚糖结合物， 已经表征了它们依赖GSH和其他硫醇依赖的荧光，并在原理上得到了证明 初步实验已经开始量化它们在活的疟疾寄生虫中的定位和强度。 DV。因此，我们唯一能够量化ARTR(青蒿素抗性)与ARTS的DV氧化还原潜力 (敏感的)寄生虫，从而第一次严格地检验了非常有吸引力的假设，即铁/ DCP/ARTR型寄生虫的亚铁血红素比例可能不同。这是一个关键问题，将进一步考验 对广泛接受的概念的预测，即FPIX血红素可能是基于ART的“激活剂” 毒品。此外，Fe2+PIX/Fe3+PIX降低很容易解释ARTRART药物效力降低的原因 寄生虫。因此，量化DV的氧化还原环境，在Hb分解代谢过程中释放FPIX，是 对于测试ART、药物药理学和耐药性的特别有吸引力的假说是必不可少的。

"Quantifying Redox Potentials for Artemisinin Resistant (ARTR) Malaria" Capitalizing on recent characterization of coumarin - based fluorescent GSH probes we have synthesized less expensive and more convenient probes including interesting morpholino derivatives and dextran conjugates, have characterized their GSH - dependent and other thiol - dependent fluorescence, and in proof - of - principle preliminary experiments have begun to quantify their localization and intensity within the live malarial parasite DV. We are thus uniquely able to quantify DV redox potential for ARTR (artemisinin resistant) vs ARTS (sensitive) parasites and thereby rigorously test, for the first time, the very attractive hypothesis that ferric / ferrous heme ratios may differ for DCP/ARTR parasites. This is an essential issue that further tests the predictions of the widely accepted concept that FPIX heme is the likely "activator" of ART - based drugs. Furthermore, reduced Fe2+PIX / Fe3+PIX would easily explain reduced ART drug potency in ARTR parasites. Thus, quantifying redox environment of the DV, where FPIX is released during Hb catabolism, is essential for testing particularly attractive hypotheses for ART drug pharmacology and resistance.