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.

Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice / J. Konstantinović, M. Videnović, S. Orsini, K. Bogojević, S. D'Alessandro, D. Scaccabarozzi, N. Terzić Jovanović, L. Gradoni, N. Basilico, B.A. Šolaja. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 9:7(2018 Jul 12), pp. 629-634. [10.1021/acsmedchemlett.8b00053]

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

S. D'Alessandro;D. Scaccabarozzi;N. Basilico
Penultimo
;
2018-07-12

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.
Leishmania infantum; promastigote; amastigote; mice model; aminoquinoline
Settore MED/04 - Patologia Generale
Settore MED/07 - Microbiologia e Microbiologia Clinica
Towards multi-stage drugs to fight poverty related and neglected parasitic diseases: synthetic and natural compounds directed against Leishmania, Plasmodium and Schistosoma life stages and assessment of their mechanisms of action.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/611412
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