Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents
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 r...
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2019
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00452068_v83_n_p526_Chanquia http://hdl.handle.net/20.500.12110/paper_00452068_v83_n_p526_Chanquia |
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paper:paper_00452068_v83_n_p526_Chanquia2023-06-08T15:05:12Z Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents 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 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. 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00452068_v83_n_p526_Chanquia http://hdl.handle.net/20.500.12110/paper_00452068_v83_n_p526_Chanquia |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| topic_facet |
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 |
| description |
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. |
| title |
Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| title_short |
Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| title_full |
Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| title_fullStr |
Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| title_full_unstemmed |
Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| title_sort |
synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
| publishDate |
2019 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00452068_v83_n_p526_Chanquia http://hdl.handle.net/20.500.12110/paper_00452068_v83_n_p526_Chanquia |
| _version_ |
1768543505738629120 |