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

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• 作者：Norma Rivera Fernández ; Mónica Mondragón Castelán…
• 刊名：Parasitology Research
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：115
• 期：5
• 页码：2081-2096
• 全文大小：1,775 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Medical Microbiology
  Microbiology
  Immunology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1955
• 卷排序：115

文摘

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.KeywordsApicomplexanToxoplasma gondiiPellicleQuinoxalinone derivativesIn silico drug designTOMOCOMD-CARDD