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

NORMA RIVERA; M. MONDRAGON-CASTELÁN; S. GONZÁLEZ-POZOS; C. J. RAMIREZ FLORES; R. MONDRAGÓN-GONZALEZ; Y. MARRERO PONCE; V.J. ARÁN; M.A .MARTINS ALHO; R. MONDRAGÓN-FLORES

PARASITOLOGY RESEARCH

SPRINGER

Lugar: Berlin; Año: 2016 vol. 115 p. 2081 - 2096

0932-0113

Quinoxalinone derivatives, identified as VAM2compounds (7-nitroquinoxalin-2-ones), were evaluatedagainst Toxoplasma gondii tachyzoites of the RH strain. TheVAM2 compounds were previously synthesized based on thedesign obtained from an in silico prediction with the softwareTOMOCOMD-CARDD. From the ten VAM2 drugs tested,several showed a deleterious effect on tachyzoites. However,VAM2-2 showed the highest toxoplasmicidal activity generatinga remarkable decrease in tachyzoite viability (in about91 %) and a minimal alteration in the host cell. An evidentinhibition of host cell invasion by tachyzoites previouslytreated with VAM2-2 was observed in a dose-dependent manner.In addition, remarkable alterations were observed in thepellicle parasite, such as swelling, roughness, and blebbing.Toxoplasma motility was inhibited, and subpellicular cytoskeletonintegrity was altered, inducing a release of its componentsto the soluble fraction. VAM2-2 showed a clear andspecific deleterious effect on tachyzoites viability, structuralintegrity, and invasive capabilities with limited effects in hostcells morphology and viability. VAM2-2 minimum inhibitoryconcentration (MIC50) was determined as 3.3 μM ± 1.8.Effects of quinoxalinone derivatives on T. gondii provide thebasis for a future therapeutical alternative in the treatment oftoxoplasmosis