Winter R W, Cornell K A, Johnson L L, Ignatushchenko M, Hinrichs D J, Riscoe M K
Medical Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon 97201, USA.
Antimicrob Agents Chemother. 1996 Jun;40(6):1408-11. doi: 10.1128/AAC.40.6.1408.
We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar analysis was approximately 60-fold for experiments initiated with asynchronous parasites. The most pronounced synergism was observed in experiments with synchronized trophozoite-infected erythrocytes, in which the degree of synergy was at least 300-fold. While the mechanism underlying this drug potentiation remains unresolved, it is hypothesized that rufigallol acts in pro-oxidant fashion to produce oxygen radicals inside parasitized erythrocytes. These radicals would attack exifone, thereby initiating its transformation into a more potent compound, a xanthone.
我们发现了卢非咯尔与结构相似的化合物艾西酚之间显著的协同抗疟相互作用。这种协同效应在恶性疟原虫的氯喹敏感和氯喹抗性克隆中均有产生。通过标准等效应线分析估计，对于以非同步寄生虫开始的实验，增效程度约为60倍。在同步滋养体感染红细胞的实验中观察到最显著的协同作用，其中协同程度至少为300倍。虽然这种药物增效的潜在机制仍未解决，但据推测，卢非咯尔以促氧化剂的方式起作用，在被寄生的红细胞内产生氧自由基。这些自由基会攻击艾西酚，从而引发其转化为一种更有效的化合物——呫吨酮。
