A minimalistic approach to develop new anti-apicomplexa polyamines analogs.
A minimalistic approach to develop new anti-apicomplexa polyamines analogs.
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开发新的抗 apicomplexa 多胺类似物的简约方法。
DOI：
10.1016/j.ejmech.2017.11.069
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发表时间：
2018
影响因子：
6.7
通讯作者：
Labadie,GuillermoR
中科院分区：
文献类型：
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作者：
Panozzo-Zénere,EstebanA;Porta,ExequielOJ;Arrizabalaga,Gustavo;Fargnoli,Lucía;Khan,ShabanaI;Tekwani,BabuL;Labadie,GuillermoR
迫切需要开发新的化学实体来防治由寄生虫引起的主要疾病。利用化学信息学工具，采用极简方法制备了30个二胺类似物库，并对其对顶复合体寄生虫的作用进行了评价。N′-二取代脂肪二胺系列的不同成员在亚微摩尔浓度下对刚地弓形虫和对氯喹敏感和耐药的恶性疟原虫显示出高水平的选择性和体外活性。为了证明仲胺的重要性，我们合成了十N，N,N ',N ' -四取代脂肪族二胺衍生物，它们的活性明显低于它们的二取代对应物。进行了理论研究，以确定控制化合物活性的电子因素。
The development of new chemical entities against the major diseases caused by parasites is highly desired. A library of thirty diamines analogs following a minimalist approach and supported by chemoinformatics tools have been prepared and evaluated against apicomplexan parasites. Different member of the series ofN,N′-disubstituted aliphatic diamines shownin vitroactivities at submicromolar concentrations and high levels of selectivity against Toxoplasma gondii and in chloroquine-sensitive and resistant-strains of Plasmodium falciparum. In order to demonstrate the importance of the secondary amines, tenN,N,N′,N′-tetrasubstituted aliphatic diamines derivatives were synthesized being considerably less active than their disubstituted counterpart. Theoretical studies were performed to establish the electronic factors that govern the activity of the compounds.