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

Abstract

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 TgCDPK1 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.

Elucidating the biological activities of thiadazole derivatives against Vibrio cholerae: Insights from DFT, spectroscopic studies, molecular docking and ADMET

“…These ndings indicate that TDZD in DMSO and TDZD in water had a value of 1632 cm ¹, TDZD in ethanol had a value of 1645 cm ¹, and TDZD in gas had a value of 1640 cm ¹. In simpler terms, the compounds exhibited similar stabilities in the presence of TDZD in DMSO and in the presence of TDZD in water and different stabilities in the presence of ethanol and gas, suggesting that these compounds are less stable than the other phases [24]. Generally, the symmetric stretching and various identi ed functional groups highlighted in this context indicate good stability of the compound.…”

“…The molecular docking process is a computational technique that predicts the binding mode and binding a nity of small molecules, such as drug candidates, to a target protein. Autodock tools and AutoDock Vina 1.5.6 [24] are widely used software tools for performing molecular docking simulations. In this study, TDZD was docked with two selected proteins, namely, IXTC and 6EHB, which are CTRs obtained from a protein database (https://www.rcsb.org/).…”

Decorative Multi-Walled Carbon Nanotubes by ZnO: Synthesis, Characterization, and Potent Anti-Toxoplasmosis Activity

“…Cytokines levels namely (TNF-α, IL-10, IL-6, and IL-1B) in T. gondii-infected mouse serum were determined according to the manufacturer's instructions and through the use of enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA). At 450 nm, the response was measured using a microplate reader (Absorbance 96, Byonoy, Hamburg, Germany) [26].…”

“…Specimens from diverse organs (brain, liver, and spleen) were fixated in 10% formalin, dehydrated in successive grades of ethanol, rinsed in xylol, and then imbedded in paraffin wax. Staining of each specimen was utilized by Ehrlich's hematoxylin and eosin (H&E) stain [26].…”

“…Ingestion of oocysts (from a cat's faeces or undercooked meat), preceeded by the emergence of sporozoites and bradyzoites from the consumed oocysts. The emerged sporozoites and bradyzoites will penetrate the human intestinal cells, where they will be transformed into tachyzoites [26]. Through the blood or lymphatic system, the tachyzoites will subsequently disseminate to other organs.…”