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.
|Titolo:||Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice|
BASILICO, NICOLETTA (Penultimo) (Corresponding)
|Parole Chiave:||Leishmania infantum; promastigote; amastigote; mice model; aminoquinoline|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore MED/07 - Microbiologia e Microbiologia Clinica
|Progetto:||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.|
|Data di pubblicazione:||12-lug-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acsmedchemlett.8b00053|
|Appare nelle tipologie:||01 - Articolo su periodico|