Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax
Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax
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DOI：
10.1128/aac.00874-15
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发表时间：
2015-07
影响因子：
4.9
通讯作者：
Grennady Wirjanata;Boni F. Sebayang;Ferryanto Chalfein;Prayoga;Irene Handayuni;Leily Trianty;E. Kenangalem;Rintis Noviyanti;B. Campo;J. Poespoprodjo;J. Möhrle;Richard N. Price;Richard N. Price;J. Marfurt
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文献类型：
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作者：
Grennady Wirjanata;Boni F. Sebayang;Ferryanto Chalfein;Prayoga;Irene Handayuni;Leily Trianty;E. Kenangalem;Rintis Noviyanti;B. Campo;J. Poespoprodjo;J. Möhrle;Richard N. Price;Richard N. Price;J. Marfurt
摘要4-氨基喹啉萘酚(NQ)和噻嗪染料亚甲基蓝(MB)对恶性疟原虫有较强的体外抗疟作用，但对间日疟的敏感性数据有限。在印度尼西亚巴布亚的临床现场分离株上，用一种改进的裂殖体成熟试验评估了NQ和MB的物种和阶段特异性的体外活性，那里的恶性疟原虫和间日疟原虫流行着多重耐药。两个化合物对恶性疟原虫和间日疟原虫均有较高的抑制活性(半数抑制浓度[IC50]：NQ，8.0 nM[2.6~71.8 nM]；MB，1.6 nM[0.2~7.0 nM])和间日疟原虫(NQ，7.8 nM[1.5~34.2 nM]；MB，1.2 nM[0.4~4.3 nM])。不同阶段的药敏试验显示，滋养体阶段暴露的寄生虫对恶性疟原虫和间日疟原虫的IC50值分别为26.5vs5.1nM(P=0.021)和341.6 nM(P=0.021)，间日疟原虫对MB的IC50值分别为10.1nM和1.6nM(P=0.010)。NQ和MB对恶性疟原虫和间日疟原虫具有良好的体外活性，突显了它们在这两个物种流行的地区治疗耐多药疟疾的潜在效用。
ABSTRACT The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC50]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC50s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.