文献类型：期刊文献

英文题名：Dietary flavonoids fisetin and myricetin: Dual inhibitors of Plasmodium falciparum falcipain-2 and plasmepsin II

作者：Jin, Huangtao[1];Xu, Zhongyu[1];Cui, Kunqiang[1];Zhang, Tianshu[1];Lu, Weiqiang[2,3];Huang, Jin[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]E China Normal Univ, Inst Biomed Sci, Shanghai 200241, Peoples R China;[3]E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China

年份：2014

卷号：94

起止页码：55

外文期刊名：FITOTERAPIA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000335608700007)】；

基金：This work was supported by the National Natural Science Foundation of China (81102420), the Shanghai Committee of Science and Technology (Grant 11DZ2260600) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Dietary flavonoids; Falcipain-2; Plasmepsin Il; Dual inhibitor

摘要：Malaria is one of the most devastating infectious diseases in the developing world. Until now, only one candidate malaria vaccine RTS,S/AS01 has shown modest protection in phase 3 trial in African infants. Hence the treatment of malaria still depends on the current chemotherapeutic drugs. Considering the resistance of malaria parasites to almost all used antimalarial drugs, aiming at multi-targets rather than a single target will be a more promising strategy. Previous studies have shown that myricetin and fisetin exhibited in vitro antimalarial activity against Plasmodium falciparum, but very little research focused on the molecular mechanism for their parasiticidal activity. The cysteine protease falcipain-2 and aspartic protease plasmepsin II have long been considered as important antimalarial drug targets, especially combined inhibition of these two proteases. In this study, we determined that myricetin and fisetin are dual inhibitors of falcipain-2 and plasmepsin II, which might account for their antimalarial properties. Overall, the dual inhibition of falcipain-2 and plasmepsin II by myricetin and fisetin has shed light on a possible mechanism for their antimalarial activity and provided a rationale for further development as antimalarial drugs. (C) 2014 Elsevier B.V. All rights reserved.