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Abstract:

As a part of our project aimed at developing new safe chemotherapeutic agents against tropical diseases, a series of aryl derivatives of 2- and 3-aminoquinoline, some of them new compounds, was designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis (Chagas’ disease), and Leishmania mexicana, the etiological agent of Leishmaniasis. Some of them showed a remarkable activity as parasite growth inhibitors. Fluorine-containing derivatives 11b and 11c were more than twice more potent than geneticin against intracellular promastigote form of Leishmania mexicana exhibiting both IC 50 values of 41.9 μM. The IC 50 values corresponding to fluorine and chlorine derivatives 11b–d were in the same order than benznidazole against epimastigote form. These drugs are interesting examples of effective antiparasitic agents with outstanding potential not only as lead drugs but also to be used for further in vivo studies. In addition, the obtained compounds showed no toxicity in Vero cells, which makes them good candidates to control tropical diseases. Regarding the probable mode of action, assayed quinoline derivatives interacted with hemin, inhibiting its degradation and generating oxidative stress that is not counteracted by the antioxidant defense system of the parasite. © 2018 Elsevier Inc.

Registro:

Documento: Artículo
Título:Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents
Autor:Chanquia, S.N.; Larregui, F.; Puente, V.; Labriola, C.; Lombardo, E.; García Liñares, G.
Filiación:Laboratorio de Biocatálisis. Departamento de Química Orgánica y UMYMFOR, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, piso 3, C1428EGA Buenos Aires, Argentina
Centro de Investigaciones sobre Porfirias y Porfirinas (CIPYP, UBA-CONICET), Hospital de Clínicas José de San Martín, Avenida Córdoba 2351, Buenos Aires, 1120, Argentina
Instituto de Investigaciones Bioquímicas, Av. Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina
Palabras clave:Chagas’ disease; Hemin interaction; Leishmaniasis; Oxidative damage; Quinoline derivatives; 2 (2 fluor phenylamino)quinoline; 2 (3 fluor phenylamino)quinoline; 2 (4 carboxy phenylamino)quinoline; 2 (4 chloro phenylamino)quinoline; 2 (4 fluor phenylamino)quinoline; 2 (4 vinyl phenylamino)quinoline; 3 (2 fluor phenylamino)quinoline; 3 (3 fluor phenylamino)quinoline; 3 (4 carboxy phenylamino)quinoline; 3 (4 chloro phenylamino)quinoline; 3 (4 fluor phenylamino)quinoline; antibiotic g 418; antileishmanial agent; antimitotic agent; antitrypanosomal agent; benznidazole; cytotoxic agent; hemin; quinoline derivative; thiol group; unclassified drug; animal cell; antiproliferative activity; antiprotozoal activity; Article; arylation; binding assay; CC50; controlled study; cytotoxicity assay; drug cytotoxicity; drug design; drug structure; drug synthesis; epimastigote; growth inhibition; IC50; in vitro study; isomer; Leishmania mexicana; nonhuman; oxidation reduction state; oxidative stress; percentage of viable cells; priority journal; promastigote; Trypanosoma cruzi; Vero cell line
Año:2019
Volumen:83
Página de inicio:526
Página de fin:534
DOI: http://dx.doi.org/10.1016/j.bioorg.2018.10.053
Título revista:Bioorganic Chemistry
Título revista abreviado:Bioorg. Chem.
ISSN:00452068
CODEN:BOCMB
CAS:antibiotic g 418, 49863-47-0, 83855-92-9; benznidazole, 22994-85-0; hemin, 16009-13-5
Registro:http://digital.bl.fcen.uba.ar/collection/paper/document/paper_00452068_v83_n_p526_Chanquia

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Citas:

---------- APA ----------
Chanquia, S.N., Larregui, F., Puente, V., Labriola, C., Lombardo, E. & García Liñares, G. (2019) . Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents. Bioorganic Chemistry, 83, 526-534.
http://dx.doi.org/10.1016/j.bioorg.2018.10.053
---------- CHICAGO ----------
Chanquia, S.N., Larregui, F., Puente, V., Labriola, C., Lombardo, E., García Liñares, G. "Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents" . Bioorganic Chemistry 83 (2019) : 526-534.
http://dx.doi.org/10.1016/j.bioorg.2018.10.053
---------- MLA ----------
Chanquia, S.N., Larregui, F., Puente, V., Labriola, C., Lombardo, E., García Liñares, G. "Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents" . Bioorganic Chemistry, vol. 83, 2019, pp. 526-534.
http://dx.doi.org/10.1016/j.bioorg.2018.10.053
---------- VANCOUVER ----------
Chanquia, S.N., Larregui, F., Puente, V., Labriola, C., Lombardo, E., García Liñares, G. Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents. Bioorg. Chem. 2019;83:526-534.
http://dx.doi.org/10.1016/j.bioorg.2018.10.053