Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice

ACS Med Chem Lett. 2018 May 4;9(7):629-634. doi: 10.1021/acsmedchemlett.8b00053. eCollection 2018 Jul 12.


In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50 < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 μM against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.