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

Jelena Konstantinović; Milica Videnović; Stefania Orsini; Katarina Bogojević; Sarah D'Alessandro; Diletta Scaccabarozzi; Nataša Terzić Jovanović; Luigi Gradoni; Nicoletta Basilico; Bogdan A Šolaja

doi:10.1021/acsmedchemlett.8b00053

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.

Affiliations

¹ University of Belgrade, Faculty of Chemistry, Studentski trg 12-16, P.O. Box 51, 11158 Belgrade, Serbia.
² University of Belgrade, Faculty of Chemistry Innovative Centre, Studentski trg 12-16, 11158 Belgrade, Serbia.
³ Unit of Vector-borne Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁴ Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatrichè, Università degli Studi di Milano, Milan, Italy.
⁵ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
⁶ University of Belgrade, Institute of Chemistry, Technology, and Metallurgy, Njegoševa 12, 11000 Belgrade, Serbia.
⁷ Serbian Academy of Sciences and Arts, Knez Mihailova 35, 11158 Belgrade, Serbia.

Abstract

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.