Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication.
Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication.
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DOI：
10.1016/j.exppara.2011.02.016
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发表时间：
2011-06
影响因子：
2.1
通讯作者：
Curiel, Tyler J.
中科院分区：
文献类型：
--
作者：
Brumlik, Michael J.;Nkhoma, Standwell;Kious, Mark J.;Thompson, George R., III;Patterson, Thomas F.;Siekierka, John J.;Anderson, Tim J. C.;Curiel, Tyler J.
关键词：
我们最近证明，人p38丝裂原活化蛋白激酶（MAPK）抑制剂减少在体外和体内的复制的原生动物寄生虫弓形虫和兔脑炎原虫。在这项研究中，我们评估了五种p38 MAPK抑制剂阻断体外培养的人红细胞中恶性疟原虫复制的功效，并证明吡啶基咪唑RWJ67657和吡咯并苯并咪唑RWJ68198减少了恶性疟原虫复制，产生了在24小时时尺寸大大减小的滋养体，并且这两种药物干扰了阶段分化。有趣的是，氯喹抗性菌株W2对这些药物的敏感性明显高于氯喹敏感菌株HB3。这些结果表明，可以开发设计用于抑制人p38 MAPK活化的吡啶基咪唑和吡咯并苯并咪唑来治疗疟疾。
We recently demonstrated that human p38 mitogen-activated protein kinase (MAPK) inhibitors reduced in vitro and in vivo replication of the protozoan parasites Toxoplasma gondii and Encephalitozoon cuniculi. In this study, we assessed the efficacy of five p38 MAPK inhibitors to block the replication of Plasmodium falciparum in human erythrocytes cultured ex vivo and demonstrate that the pyridinylimidazole RWJ67657 and the pyrrolobenzimidazole RWJ68198 reduced Plasmodium falciparum replication, yielded trophozoites that were greatly diminished in size at 24 h, and that these two agents interfered with stage differentiation. Interestingly, the chloroquine-resistant strain W2 was significantly more sensitive to these drugs than was the chloroquine-sensitive strain HB3. These results suggest that pyridinylimidazoles and pyrrolobenzimidazoles designed to inhibit human p38 MAPK activation can be developed to treat malaria.
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影响因子：
64.8
作者：
Gamo, Francisco-Javier;Sanz, Laura M.;Garcia-Bustos, Jose F.
通讯作者：
Garcia-Bustos, Jose F.
DOI：
10.1073/pnas.95.13.7422
发表时间：
1998-06-23
影响因子：
11.1
作者：
Shapiro, L;Heidenreich, KA;Dinarello, CA
通讯作者：
Dinarello, CA
影响因子：
27.4
作者：
Hammaker D;Firestein GS
通讯作者：
Firestein GS
DOI：
10.1155/2011/971968
发表时间：
2011
期刊：
Journal of signal transduction
影响因子：
--
作者：
Brumlik MJ;Pandeswara S;Ludwig SM;Murthy K;Curiel TJ
通讯作者：
Curiel TJ
影响因子：
2.7
作者：
Biftu, T;Feng, D;Wyvratt, M
通讯作者：
Wyvratt, M