Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice,ACS Medicinal Chemistry Letters

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Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2018-05-04 00:00:00 , DOI: 10.1021/acsmedchemlett.8b00053
Jelena Konstantinović ₁ , Milica Videnović ₂ , Stefania Orsini ₃ , Katarina Bogojević ₁ , Sarah D’Alessandro ₄ , Diletta Scaccabarozzi ₅ , Nataša Terzić Jovanović ₆ , Luigi Gradoni ₃ , Nicoletta Basilico ₁ , Bogdan A. Šolaja _{1,

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Affiliation

In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC₅₀ < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC₅₀ < 1 μM against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.

中文翻译：

新型氨基喹啉衍生物显着降低婴儿利什曼原虫感染小鼠的寄生虫负荷

在这封信中，已经对30种基于4-氨基喹啉的化合物作为抗衰老药物的潜力进行了详细分析。表明IC 10个化合物₅₀ <1μM的对的前鞭毛体阶段婴儿利什曼原虫和L. tropica，以及五个化合物显示IC ₅₀ <1μM的对intramacrophage婴儿利什曼原虫无鞭毛体。两种化合物显示出骨髓衍生的巨噬细胞对NO和ROS的剂量依赖性增强作用，并且体内寄生虫负荷显着降低，具有短期和口服活性。据我们所知，这是在婴儿利什曼原虫中有活性的4-氨基-7-氯喹啉衍生物的第一个实例被感染的小鼠。

更新日期：2018-05-04

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