Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents |
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| Institution: | 1. 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;2. Centro de Investigaciones sobre Porfirias y Porfirinas (CIPYP, UBA-CONICET), Hospital de Clínicas José de San Martín, Avenida Córdoba 2351, 1120 Buenos Aires, Argentina;3. Instituto de Investigaciones Bioquímicas, Av. Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina;1. Laboratorio de Ingeniería Genética, Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, San Luis, Caracas, Venezuela;2. Cátedra de Química General, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1041-A, Venezuela;1. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;2. Department of Chemistry, Hazara University, Mansehra 21300, Pakistan;3. Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;4. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia;5. College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;1. Programa de Maestría y Doctorado en Ciencias Químicas, UNAM, México, DF 04510, Mexico;2. Facultad de Química, Departamento de Farmacia, UNAM, México, DF 04510, Mexico;3. Escuela Superior de Medicina, Laboratorio de Modelado Molecular y Bioinformática de la SEPI, IPN, México, DF 11340, Mexico;4. Escuela Nacional de Ciencias Biológicas, Departamento de Parasitología, IPN, México, DF 11340, Mexico;5. Departamento de Infectología, Instituto Nacional de Perinatología, México, DF 11000, Mexico;6. Tecsiquim S.A. de C.V., Toluca Estado de México 50233, Mexico;1. Department of Chemistry, Jackson State University, Jackson, MS 39217, USA;2. Department of Medical Parasitology & Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland;3. University of Basel, Petersplatz 1, 4003 Basel, Switzerland;1. Anthem Biosciences Pvt. Ltd, 49 Bommasandra Industrial Area, Bommasandra, Bengaluru 560099, Karnataka, India;2. Foundation for Neglected Disease Research, Bengaluru 562157, Karnataka, India;3. SBST, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India |
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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 IC50 values of 41.9 μM. The IC50 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. |
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| Keywords: | Quinoline derivatives Leishmaniasis Chagas’ disease Hemin interaction Oxidative damage |
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