Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents

CHANQUIA, SANTIAGO N.; LARREGUI, FACUNDO; PUENTE, VANESA; LABRIOLA, CARLOS; LOMBARDO, ELISA; GARCÍA LIÑARES, GUADALUPE

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2019 vol. 83 p. 526 - 534

0045-2068

A B S T R A C TAs a part of our project aimed at developing new safe chemotherapeutic agents against tropical diseases, a seriesof aryl derivatives of 2- and 3-aminoquinoline, some of them new compounds, was designed, synthesized, andevaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis(Chagas? disease), and Leishmania mexicana, the etiological agent of Leishmaniasis. Some of themshowed a remarkable activity as parasite growth inhibitors. Fluorine-containing derivatives 11b and 11c weremore than twice more potent than geneticin against intracellular promastigote form of Leishmania mexicanaexhibiting both IC50 values of 41.9 μM. The IC50 values corresponding to fluorine and chlorine derivatives 11b?dwere in the same order than benznidazole against epimastigote form. These drugs are interesting examples ofeffective antiparasitic agents with outstanding potential not only as lead drugs but also to be used for further invivo studies. In addition, the obtained compounds showed no toxicity in Vero cells, which makes them goodcandidates to control tropical diseases. Regarding the probable mode of action, assayed quinoline derivativesinteracted with hemin, inhibiting its degradation and generating oxidative stress that is not counteracted by theantioxidant defense system of the parasite.