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蒿甲醚醚衍生物——新型青蒿素衍生物的抗疟原虫活性及其对约氏疟原虫感染小鼠发病机制的影响。

Antiplasmodial activity of artecyclopentyl mether a new artemisinin derivative and its effect on pathogenesis in Plasmodium yoelii nigeriensis infected mice.

机构信息

Central Institute of Medicinal and Aromatic Plants, CSIR, P.O.CIMAP, 226015 Lucknow, India.

出版信息

Parasitol Res. 2011 Oct;109(4):1003-8. doi: 10.1007/s00436-011-2344-1. Epub 2011 May 4.

Abstract

In an effort to evaluate novel derivatives from artemisinin, possessing potential antimalarial activity, a new derivative artecyclopentyl mether (CPM-1) was derivatized and evaluated for its dose-dependent efficacy in Plasmodium yoelii nigeriensis infected mice. The survivability of mice at 7.5 mg/kg was >28 days with negligible parasitaemia and recovered anemia (66.16-72.62%). Artecyclopentyl mether was also found to modulate the pro- and anti-inflammatory cytokines (IFN-γ, 39.64-56.92%; TNF, 49.10-74.31%; IL-4, 11.53-43.22%; IL-10, 37.60-53.52%) favourably besides optimizing the oxidative stress to the infected subjects as evident by the nitric oxide (88.76-95.43%), lipid peroxidation (59.30-76.05%) and glycaemic data (62.70-76.66%). The results indicate the potentiality of the new derivative as an antimalarial against asexual stages of the parasite.

摘要

为了评估具有抗疟活性的青蒿素新衍生物,合成了一种新的衍生物 artecyclopentyl mether(CPM-1),并对其在感染 Plasmodium yoelii nigeriensis 的小鼠中的剂量依赖性疗效进行了评估。在 7.5mg/kg 剂量下,小鼠的存活率>28 天,寄生虫血症可忽略不计,贫血得到恢复(66.16-72.62%)。artecyclopentyl mether 还被发现可以调节促炎和抗炎细胞因子(IFN-γ,39.64-56.92%;TNF,49.10-74.31%;IL-4,11.53-43.22%;IL-10,37.60-53.52%),同时使感染宿主的氧化应激得到优化,如一氧化氮(88.76-95.43%)、脂质过氧化(59.30-76.05%)和血糖数据(62.70-76.66%)所示。这些结果表明,这种新的衍生物具有作为抗疟药物对抗寄生虫无性阶段的潜力。

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