Exploring the Antiparasitic Activity of Tris -1,3,4-Thiadiazoles against Toxoplasma gondii -Infected Mice.

Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain tris -1,3,4-thiadiazole derivatives ( 6 , 7 ) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti- Toxoplasma gondii agents have been conducted and reported in vitro. However, this is the first study to test the anti- Toxoplasma gondii activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of T. gondii . All the observed results demonstrated compound ( 7 )'s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against Tg CDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound 7 's higher potency compared to compound 6 and megazol. According to the mentioned results, tris -1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of T. gondii .