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

• DOI: 10.1007/s00436-016-4953-1
• Publication Date: 2016-02-17T23:21:41Z
• Authors: Norma Rivera Fern...; Mónica Mondragón ...; Sirenia González ...; Carlos J. Ramírez...; Ricardo Mondragón...; Carmen T. Gómez d...; Kitzia N. Castro ...; Yovani Marrero Ponce; Vicente J. Arán; Miriam A. Martins...; Ricardo Mondragón...
• Keywords: 0301 basic medicine; Mice; Mice, Inbred BALB C; 03 medical and health sciences; Cell Line, Tumor; Quinoxalines; Animals; Humans; Toxoplasma; Cytoskeleton; Toxoplasmosis; 3. Good health

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.