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Rivera Fernández, N.; Mondragón Castelán, M.; González Pozos, S.; Ramírez Flores, C.J.; Mondragón González, R.; Gómez de León, C.T.; Castro Elizalde, K.N.; Marrero Ponce, Y.; Arán, V.J.; Martins Alho, M.A.; Mondragón Flores, R. "A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro" (2016) Parasitology Research. 115(5):2081-2096
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Abstract:

Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis. © 2016, Springer-Verlag Berlin Heidelberg.

Registro:

Documento: Artículo
Título:A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro
Autor:Rivera Fernández, N.; Mondragón Castelán, M.; González Pozos, S.; Ramírez Flores, C.J.; Mondragón González, R.; Gómez de León, C.T.; Castro Elizalde, K.N.; Marrero Ponce, Y.; Arán, V.J.; Martins Alho, M.A.; Mondragón Flores, R.
Filiación:Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, 07360 DF, Mexico
Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero07360 DF, Mexico
Unidad de Microscopía Electrónica (LANSE), CINVESTAV, DF, Mexico
Departamento de Genética y Biología Molecular, CINVESTAV, DF, Mexico
Edificio de Especialidades Médicas, Hospital de los Valles, Colegio de Ciencias de la Salud, Universidad de San Francisco de Quito, Av. Interoceánica Km 12 1/2 Cumbayá, Quito, Ecuador
Instituto de Química Médica, CSIC, c/ Juan de la Cierva 3, Madrid, 28006, Spain
Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR-CONICET), Departamento de Química Orgánica, FCEN y LabMOr – INTECIN, FI, UBA, Paseo Colón 850, 5to. Piso, Buenos Aires, CP C1063ACV, Argentina
Palabras clave:Apicomplexan; In silico drug design; Pellicle; Quinoxalinone derivatives; TOMOCOMD-CARDD; Toxoplasma gondii; antiprotozoal agent; quinoxalinone derivative; unclassified drug; vam 2 1; vam 2 10; vam 2 2; vam 2 3; vam 2 4; vam 2 5; vam 2 6; vam 2 7; vam 2 8; vam 2 9; quinoxaline derivative; animal experiment; animal model; antiprotozoal activity; Article; cell motility; computer model; electron microscopy; host cell; human; human cell; larynx squamous cell carcinoma; minimum inhibitory concentration; mouse; nonhuman; priority journal; tachyzoite; Toxoplasma gondii; transmission electron microscopy; animal; Bagg albino mouse; cytoskeleton; drug effects; parasitology; physiology; Toxoplasma; toxoplasmosis; tumor cell line; ultrastructure; Animals; Cell Line, Tumor; Cytoskeleton; Humans; Mice; Mice, Inbred BALB C; Quinoxalines; Toxoplasma; Toxoplasmosis
Año:2016
Volumen:115
Número:5
Página de inicio:2081
Página de fin:2096
DOI: http://dx.doi.org/10.1007/s00436-016-4953-1
Título revista:Parasitology Research
Título revista abreviado:Parasitol. Res.
ISSN:09320113
CODEN:PARRE
CAS:Quinoxalines
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09320113_v115_n5_p2081_RiveraFernandez

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Citas:

---------- APA ----------
Rivera Fernández, N., Mondragón Castelán, M., González Pozos, S., Ramírez Flores, C.J., Mondragón González, R., Gómez de León, C.T., Castro Elizalde, K.N.,..., Mondragón Flores, R. (2016) . A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro. Parasitology Research, 115(5), 2081-2096.
http://dx.doi.org/10.1007/s00436-016-4953-1
---------- CHICAGO ----------
Rivera Fernández, N., Mondragón Castelán, M., González Pozos, S., Ramírez Flores, C.J., Mondragón González, R., Gómez de León, C.T., et al. "A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro" . Parasitology Research 115, no. 5 (2016) : 2081-2096.
http://dx.doi.org/10.1007/s00436-016-4953-1
---------- MLA ----------
Rivera Fernández, N., Mondragón Castelán, M., González Pozos, S., Ramírez Flores, C.J., Mondragón González, R., Gómez de León, C.T., et al. "A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro" . Parasitology Research, vol. 115, no. 5, 2016, pp. 2081-2096.
http://dx.doi.org/10.1007/s00436-016-4953-1
---------- VANCOUVER ----------
Rivera Fernández, N., Mondragón Castelán, M., González Pozos, S., Ramírez Flores, C.J., Mondragón González, R., Gómez de León, C.T., et al. A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro. Parasitol. Res. 2016;115(5):2081-2096.
http://dx.doi.org/10.1007/s00436-016-4953-1