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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todo:paper_09320113_v115_n5_p2081_RiveraFernandez2023-10-03T15:48:19Z A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro 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. 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 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. Fil:Martins Alho, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09320113_v115_n5_p2081_RiveraFernandez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Rivera Fernández, N. |
| title |
A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro |
| title_short |
A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro |
| title_full |
A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro |
| title_fullStr |
A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro |
| title_full_unstemmed |
A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro |
| title_sort |
new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of toxoplasma gondii tachyzoites in vitro |
| url |
http://hdl.handle.net/20.500.12110/paper_09320113_v115_n5_p2081_RiveraFernandez |
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