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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Detalles Bibliográficos
Autores principales: 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.
Formato: JOUR
Materias:
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
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
Toxoplasmosis
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_09320113_v115_n5_p2081_RiveraFernandez
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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