Three series of new imidazole‐fused imidazo[2,1‐b][1,3,4]thiadiazole analogues (compounds 20 a–g, 21 a–g, and 22 a–g) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram‐positive and ‐negative bacteria. N‐((4‐(2‐Cyclopropyl‐6‐(4‐fluorophenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)‐5‐(6‐methyl‐pyridin‐2‐yl)‐1H‐imidazol‐2‐yl)methyl)aniline (21 a) showed the highest activity against C. albicans (MIC50=0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast‐1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.

Nineteen mycophenolic acid (MPA) derivatives were designed and synthesized, and their anti-Toxoplasma activity evaluated for the rst time. Among them, N-propylimidazole-modi ed compound E5 demonstrated the strongest activity, and the IC 50 against HFF-1 (Human Foreskin Fibroblasts-1) cells following infection with T. gondii is 80.9 μM (MPA-211.5 μM) and its selectivity value is 2.2 (MPA-1.2). In vivo experiments, E5 signi cantly inhibited the proliferation of tachyzoites in the abdominal cavity of mice acutely infected with T. gondii (inhibition rates 46.7%), and this inhibitory effect was greater than that of spiramycin (inhibition rates 31.3%) and MPA (inhibition rates 15.9%), this indicated that E5 had signi cant protective effects on the host during acute Toxoplasma infection. In addition E5 signi cantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of infected mice, signi cantly increased the level of glutathione (GSH) in the liver, and signi cantly reduced the level of malondialdehyde (MDA), indicating that it has a signi cant hepatoprotective effect against T. gondii infection. Similarly, E5 can relieve hepatomegaly and splenomegaly induced by acute Toxoplasma infection. Spiramycin aggravated appetite loss in infected mice, while E5 did not. In summary, the results indicated that E5 has potential as a candidate anti-T. gondii drug.

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

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