Synthesis and evaluation of in vitro and in vivo anti-Toxoplasma gondii activity of tetraoxane-substituted ursolic acid derivatives

A series of derivatives of ursolic acid (UA) were synthesised, the anti-Toxoplasma gondii activity was tested, and the selectivity index (SI) of these compounds was calculated to determine the derivative with the best anti-Toxoplasma gondii activity. Compound A7 showed the best activity against the Toxoplasma gondii (IC50 in T. gondii infected GES-1 cells: 9.1 +/- 7.2 mu M), better than the lead compound UA and the positive control drug Spiramycin. Compound A7 was selected for further in vivo research: A7 was tested for its effect on the inhibition rate of tachyzoites in mice and its biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde were determined. Compound A7 was evaluated for its anti-Toxoplasma activity and partial damage to the liver. Therefore, the results show that compound A7 could be a potential lead compound for developing a novel anti-Toxoplasma gondii molecule.

Automated summary

The derivatives of ursolic acid (UA) were synthesized and tested for their anti-Toxoplasma gondii activity. Compound A7 showed the best activity, surpassing both UA and the positive control drug Spiramycin. Further research revealed that A7 had an impact on the inhibition rate of tachyzoites in mice and caused some damage to the liver. These findings suggest that A7 could be a potential lead compound for developing a novel anti-Toxoplasma gondii molecule.