Design, synthesis and biological evaluation of antiparasitic dinitroaniline-ether phospholipid hybrids
作者:Marina Roussaki、George E. Magoulas、Theano Fotopoulou、Nuno Santarem、Emile Barrias、Ina Pöhner、Sara Luelmo、Pantelis Afroudakis、Kalliopi Georgikopoulou、Paloma Tejera Nevado、Julia Eick、Eugenia Bifeld、María J. Corral、María Dolores Jiménez-Antón、Bernhard Ellinger、Maria Kuzikov、Irini Fragiadaki、Effie Scoulica、Sheraz Gul、Joachim Clos、Kyriakos C. Prousis、Juan J. Torrado、José María Alunda、Rebecca C. Wade、Wanderley de Souza、Anabela Cordeiro da Silva、Theodora Calogeropoulou
DOI:10.1016/j.bioorg.2023.106615
日期:2023.9
length of the side chain substituent on the dinitroaniline and the choline or homocholine head group were found to affect both the activity and toxicity of the hybrids. The early ADMET profile of the derivatives did not reveal major liabilities. Hybrid 3, bearing an 11-carbon oligomethylene spacer, a butyl side chain and a choline head group, was the most potent analogue of the series. It exhibited a broad
合成了一系列九种新型醚磷脂-二硝基苯胺杂化物,旨在提供更有效的抗寄生虫药,与米替福辛相比,安全性更高。评估了化合物对婴儿乳杆菌、多诺瓦尼乳杆菌、亚马逊乳杆菌、硕大乳杆菌和热带乳杆菌前鞭毛体、婴儿乳杆菌和多诺瓦尼乳杆菌细胞内无鞭毛体、布氏锥虫以及针对不同发育阶段的体外抗寄生虫活性。克氏锥虫。发现二硝基苯胺部分和磷酸基团之间的低聚亚甲基间隔基的性质、二硝基苯胺和胆碱或高胆碱头基上的侧链取代基的长度影响杂化物的活性和毒性。衍生品的早期 ADMET 概况并未揭示主要负债。Hybrid 3带有 11 个碳低聚亚甲基间隔基、丁基侧链和胆碱头基,是该系列中最有效的类似物。它对新世界利什曼原虫属和旧世界利什曼原虫属的前鞭毛体、两种婴儿利什曼原虫菌株和多诺瓦尼利什曼原虫的细胞内无鞭毛体、对布氏利什曼原虫和克氏利什曼原虫 Y 菌株的上鞭毛体、细胞内无鞭毛体和锥鞭毛体表现出广谱抗寄生虫特性。 。早期毒性研究表明,hybrid