Synthesis and evaluation of mycophenolic acid derivatives as potential anti-Toxoplasma gondii agents

Nineteen mycophenolic acid (MPA) derivatives were designed and synthesized, their anti-Toxoplasma activity evaluated for the first time. Among them, N-propylimidazole-modified compound E5 demonstrated strongest activity, IC50 against HFF-1 (Human Foreskin Fibroblasts-1) cells following infection with T. gondii is 80.9 μM (MPA-211.5 μM) its selectivity index 2.2 (MPA-1.2). In vivo experiments, can significantly inhibit proliferation of tachyzoites in abdominal cavity mice acutely infected (inhibition rates 46.7%), this inhibitory effect was greater than that spiramycin 31.3%) MPA 15.9%), indicated had significant protective effects on host during acute Toxoplasma infection. addition, reduce levels alanine aminotransferase (ALT) aspartate (AST) serum mice, increase level glutathione (GSH) liver, malondialdehyde (MDA), indicating it has a hepatoprotective Similarly, relieve hepatomegaly splenomegaly induced by Spiramycin aggravated appetite loss while did not. summary, results potential as candidate anti-T. drug.