PDF(Pubmed)
Abstract：
Nagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma, are diseases that impede human and animal health, and economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, adverse effects, drug resistance, and difficult routes of administration. New drugs are needed. A series of 20 novel quinolone compounds with affordable synthetic routes was made and evaluated in vitro against Trypanosoma brucei and HEK293 cells. Of the 20 compounds, 12 had sub-micromolar potencies against the parasite (EC50 values=0.051-0.57 μM), and most were non-toxic to HEK293 cells (CC50 values>5 μM). Two of the most potent compounds presented sub-micromolar activities against other trypanosome (sub)species (T. cruzi and T. b. rhodesiense). Although aqueous solubility is poor, both compounds possess good logD values (2-3), and either robust or poor microsomal stability profiles. These varying attributes will be addressed in future reports.
摘要：
Nagana和人类非洲锥虫病（HAT），由锥虫（亚）种引起，是阻碍人类和动物健康的疾病，以及非洲的经济增长。少数可用的药物有缺点，包括疗效欠佳，不利影响，耐药性,和艰难的管理路线。需要新药。制备了具有负担得起的合成途径的一系列20种新型喹诺酮化合物，并在体外对布鲁氏锥虫和HEK293细胞进行了评估。在20种化合物中，12对寄生虫具有亚微摩尔效力（EC50值=0.051-0.57µM），大多数对HEK293细胞无毒（CC50值>5µM）。两种最有效的化合物对其他锥虫（亚）物种（T。克鲁兹和T.b.罗得西森)。虽然水溶性差，两种化合物都具有良好的logD值(2-3)，以及稳健或不良的微粒体稳定性。这些不同的属性将在今后的报告中讨论。
