NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria

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• 作者：Massimo Bertinaria ; Pamela Orjuela-Sanchez ; Elisabetta Marini ; Stefano Guglielmo ; Anthony Hofer ; Yuri C. Martins ; Graziela M. Zanini ; John A. Frangos ; Alberto Gasco ; Roberta Fruttero ; Leonardo J. M. Carvalho
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：October 8, 2015
• 年：2015
• 卷：58
• 期：19
• 页码：7895-7899
• 全文大小：301K
• ISSN：1520-4804

文摘

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 against Plasmodium berghei ANKA, comparable to artesunate and artemether. Hybrid 10, 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.