Bates M D, Meshnick S R, Sigler C I, Leland P, Hollingdale M R
Biomedical Research Institute, Rockville, Maryland.
Am J Trop Med Hyg. 1990 Jun;42(6):532-7. doi: 10.4269/ajtmh.1990.42.532.
The antimalarial activities of primaquine and its metabolites against exoerythrocytic (EE) stages of Plasmodium berghei in vitro were compared with their abilities to spontaneously generate activated oxygen. A quantitative relationship between the number of sporozoites and the number of EE merozoites produced was established. The reduction in the number of merozoites was used as an assay of drug activity. The ED50 of primaquine, 3.7-3.9 x 10(-6) M, was the concentration of drug that reduced the number of merozoites to 50% of controls. Several of the primaquine metabolites were much more potent than primaquine, with ED50s as low as 2 x 10(-7) M. Metabolites containing the 4-amino-1-methylbutyl side chain were most effective in vitro. Superoxide generation was measured for the various metabolites. In general, superoxide generation did not correlate with antimalarial activity. However, for the 3 metabolites with 4-amino-1-methylbutyl side chains, there was a correlation between superoxide generation and antimalarial activity.
将伯氨喹及其代谢产物对体外伯氏疟原虫红细胞外期（EE）的抗疟活性与其自发产生活性氧的能力进行了比较。建立了子孢子数量与产生的EE裂殖子数量之间的定量关系。裂殖子数量的减少用作药物活性的测定方法。伯氨喹的半数有效剂量（ED50）为3.7 - 3.9×10⁻⁶ M，即能将裂殖子数量减少至对照的50%的药物浓度。几种伯氨喹代谢产物比伯氨喹的效力更强，ED50低至2×10⁻⁷ M。含有4 - 氨基 - 1 - 甲基丁基侧链的代谢产物在体外最有效。测定了各种代谢产物的超氧化物生成情况。总体而言，超氧化物生成与抗疟活性不相关。然而，对于具有4 - 氨基 - 1 - 甲基丁基侧链的3种代谢产物，超氧化物生成与抗疟活性之间存在相关性。
