NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria.
NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria.
复制标题
NO-供体二氢青蒿素衍生物作为治疗脑型疟疾的多靶点药物。
DOI：
10.1021/acs.jmedchem.5b01036
复制
发表时间：
2015
影响因子：
7.3
通讯作者：
Carvalho,LeonardoJM
中科院分区：
文献类型：
--
作者：
Bertinaria,Massimo;Orjuela-Sanchez,Pamela;Marini,Elisabetta;Guglielmo,Stefano;Hofer,Anthony;Martins,YuriC;Zanini,GrazielaM;Frangos,JohnA;Gasco,Alberto;Fruttero,Roberta;Carvalho,LeonardoJM
双氢青蒿素支架与no供体呋喃嘧啶和NONOate部分结合的杂交产物已被合成并研究为治疗脑型疟疾（CM）的潜在工具。所设计的产品能够以一氧化氮依赖的机制扩张用苯肾上腺素预收缩的大鼠主动脉条。所有杂合物在体外和体内均表现出与青蒿琥酯和蒿甲醚相当的抗伯氏疟原虫活性。与蒿甲醚相比，选择用于其他研究的Hybrid10能够将晚期CM小鼠的存活率从27.5%提高到51.6%。青蒿素- no供体杂交化合物有望成为治疗脑型疟疾的潜在新药。
Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo againstPlasmodium bergheiANKA, comparable to artesunate and artemether. Hybrid10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.