A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro

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 t...

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Autor principal: Rivera Fernández, N.
Otros Autores: 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.
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Lenguaje:Inglés
Publicado: Springer Verlag 2016
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100 1 |a Rivera Fernández, N. 
245 1 2 |a A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro 
260 |b Springer Verlag  |c 2016 
270 1 0 |m Mondragón Flores, R.; Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, Mexico; email: rmflores@cinvestav.mx 
506 |2 openaire  |e Política editorial 
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520 3 |a 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.  |l eng 
593 |a Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, 07360 DF, Mexico 
593 |a Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero07360 DF, Mexico 
593 |a Unidad de Microscopía Electrónica (LANSE), CINVESTAV, DF, Mexico 
593 |a Departamento de Genética y Biología Molecular, CINVESTAV, DF, Mexico 
593 |a 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 
593 |a Instituto de Química Médica, CSIC, c/ Juan de la Cierva 3, Madrid, 28006, Spain 
593 |a 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 
690 1 0 |a APICOMPLEXAN 
690 1 0 |a IN SILICO DRUG DESIGN 
690 1 0 |a PELLICLE 
690 1 0 |a QUINOXALINONE DERIVATIVES 
690 1 0 |a TOMOCOMD-CARDD 
690 1 0 |a TOXOPLASMA GONDII 
690 1 0 |a ANTIPROTOZOAL AGENT 
690 1 0 |a QUINOXALINONE DERIVATIVE 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a VAM 2 1 
690 1 0 |a VAM 2 10 
690 1 0 |a VAM 2 2 
690 1 0 |a VAM 2 3 
690 1 0 |a VAM 2 4 
690 1 0 |a VAM 2 5 
690 1 0 |a VAM 2 6 
690 1 0 |a VAM 2 7 
690 1 0 |a VAM 2 8 
690 1 0 |a VAM 2 9 
690 1 0 |a QUINOXALINE DERIVATIVE 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANTIPROTOZOAL ACTIVITY 
690 1 0 |a ARTICLE 
690 1 0 |a CELL MOTILITY 
690 1 0 |a COMPUTER MODEL 
690 1 0 |a ELECTRON MICROSCOPY 
690 1 0 |a HOST CELL 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a LARYNX SQUAMOUS CELL CARCINOMA 
690 1 0 |a MINIMUM INHIBITORY CONCENTRATION 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a TACHYZOITE 
690 1 0 |a TOXOPLASMA GONDII 
690 1 0 |a TRANSMISSION ELECTRON MICROSCOPY 
690 1 0 |a ANIMAL 
690 1 0 |a BAGG ALBINO MOUSE 
690 1 0 |a CYTOSKELETON 
690 1 0 |a DRUG EFFECTS 
690 1 0 |a PARASITOLOGY 
690 1 0 |a PHYSIOLOGY 
690 1 0 |a TOXOPLASMA 
690 1 0 |a TOXOPLASMOSIS 
690 1 0 |a TUMOR CELL LINE 
690 1 0 |a ULTRASTRUCTURE 
690 1 0 |a ANIMALS 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a CYTOSKELETON 
690 1 0 |a HUMANS 
690 1 0 |a MICE 
690 1 0 |a MICE, INBRED BALB C 
690 1 0 |a QUINOXALINES 
690 1 0 |a TOXOPLASMA 
690 1 0 |a TOXOPLASMOSIS 
653 0 0 |a 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 
700 1 |a Mondragón Castelán, M. 
700 1 |a González Pozos, S. 
700 1 |a Ramírez Flores, C.J. 
700 1 |a Mondragón González, R. 
700 1 |a Gómez de León, C.T. 
700 1 |a Castro Elizalde, K.N. 
700 1 |a Marrero Ponce, Y. 
700 1 |a Arán, V.J. 
700 1 |a Martins Alho, M.A. 
700 1 |a Mondragón Flores, R. 
773 0 |d Springer Verlag, 2016  |g v. 115  |h pp. 2081-2096  |k n. 5  |p Parasitol. Res.  |x 09320113  |t Parasitology Research 
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