Grupo de Investigación, Evaluación y Desarrollo de Fármacos y Afines-IDEFARMA, Departamento de Regencia y Farmacia, Universidad de Córdoba, Montería, Córdoba, Colombia.
Programa de Estudio y Control de Enfermedades Tropicales-PECET, Facultad de Medicina, Universidad de Antioquia, Medellín, Antioquia, Colombia.
Sci Rep. 2023 Oct 16;13(1):17523. doi: 10.1038/s41598-023-43805-4.
In this study, six analogs of 2-arylquinoline were synthesized and evaluated for their in vitro and in vivo antiplasmodial and leishmanicidal activity. At a later stage, hemolytic activity and druggability were tested in vitro and in silico, respectively, observing as a result: firstly, compounds showed half-maximal effective concentration (EC) values between 3.6 and 19.3 µM. Likewise, a treatment using the compounds 4a-f caused improvement in most of the treated hamsters and cured some of them. Regarding the antiplasmodial activity, the compounds showed moderate to high activity, although they did not show hemolytic activity. Furthermore, 4e and 4f compounds were not able to control P. berghei infection when administered to animal models. Molecular dynamic simulations, molecular docking and ligand binding affinity indicate good characteristics of the studied compounds, which are expected to be active. And lastly, the compounds are absorbable at the hematoencephalic barrier but not in the gastrointestinal tract. In summary, ADMET properties suggest that these molecules may be used as a safe treatment against Leishmania.
在这项研究中，合成了六种 2-芳基喹啉类似物，并评估了它们的体外和体内抗疟原虫和杀利什曼原虫活性。在后期，分别在体外和体内进行了溶血活性和可药性测试，结果观察到：首先，化合物的半最大有效浓度 (EC) 值在 3.6 和 19.3 µM 之间。同样，使用化合物 4a-f 进行治疗可使大多数治疗后的沙鼠得到改善，并治愈了其中一些沙鼠。就抗疟原虫活性而言，这些化合物表现出中等至高的活性，尽管它们没有表现出溶血活性。此外，当将 4e 和 4f 化合物给予动物模型时，它们无法控制 P. berghei 感染。分子动力学模拟、分子对接和配体结合亲和力表明所研究的化合物具有良好的特性，有望具有活性。最后，这些化合物可被血脑屏障吸收，但不能被胃肠道吸收。总之，ADMET 特性表明这些分子可能被用作治疗利什曼病的安全疗法。
