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

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 lt 1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 lt 1 mu M 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. This is the peer-reviewed version of the following article: Konstantinović, J.; Videnović, M.; Orsini, S.; Bogojević, K.; D’Alessandro, S.; Scaccabarozzi, D.; Terzić Jovanović, N.; Gradoni, L.; Basilico, N.; Šolaja, B. A. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania Infantum Infected Mice. ACS Medicinal Chemistry Letters 2018, 9 (7), 629–634. [https://doi.org/10.1021/acsmedchemlett.8b00053] Sipplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2949]