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Eur J Med Chem. 2012 Aug;54:75-86. doi: 10.1016/j.ejmech.2012.04.029. Epub 2012 May 2.

Discovery of a new antileishmanial hit in 8-nitroquinoline series.

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  • 1Infections Parasitaires, Transmission, Physiopathologie et Thérapeutique, UMR MD3, Faculté de Pharmacie, Aix-Marseille Université, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille cedex 05, France.


A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC(50) value of 6.6 μM and CC(50) values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC(50) = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline.

Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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