喹啉衍生物的合成、杀利什曼原虫活性、结构描述符和构效关系。
Synthesis, leishmanicidal activity, structural descriptors and structure-activity relationship of quinoline derivatives.
机构信息
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, Diadema, SP, 09972-270, Brazil.
Faculdade de Medicina, Universidade de São Paulo, Av. Dr Arnaldo, 455, São Paulo, SP, 01246-903, Brazil.
出版信息
Future Med Chem. 2018 Sep 1;10(17):2069-2085. doi: 10.4155/fmc-2018-0124. Epub 2018 Aug 1.
AIM
Considering the epidemiology of leishmaniasis, the emergence of resistant parasites to the approved drugs, and severe clinical manifestations, the development of novel leishmanicidal molecules has become of considerable importance.
RESULTS
In this work, three commercially available and 19 synthesized quinoline derivatives were evaluated against promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. In addition, structural parameters and molecular electrostatic potentials were obtained by theoretical calculations, allowing statistical (principal component analyses and hierarchical cluster analyses) and comparative (molecular electrostatic potentials vs leishmanicidal activities) studies, respectively.
CONCLUSION
Principal component analyses and hierarchical cluster analyses suggested volume and polar surface area as possible structural descriptors for the leishmanicidal activity. Furthermore, a comparison between molecular electrostatic potentials and leishmanicidal activities afforded a reasonable structure-activity relationship.
目的
考虑到利什曼病的流行病学、已批准药物的耐药寄生虫的出现以及严重的临床表现，开发新型杀利什曼原虫的分子变得非常重要。
结果
在这项工作中，对三种市售和 19 种合成的喹啉衍生物进行了评估，以对抗前鞭毛体和无鞭毛体形式的亚马逊利什曼原虫（Leishmania）。此外，通过理论计算获得了结构参数和分子静电势，允许进行统计（主成分分析和层次聚类分析）和比较（分子静电势与杀利什曼原虫活性）研究。
结论
主成分分析和层次聚类分析表明，体积和极性表面积可能是杀利什曼原虫活性的结构描述符。此外，分子静电势与杀利什曼原虫活性的比较提供了合理的构效关系。
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