In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii

Abstract

Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii . Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii . The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC 50 values of 1B (0.468–0.952 μM), 2B (0.204–0.349 μM) and 3B (0.661–1.015 μM) against T. gondii . As a measure of cytotoxicity the compounds showed a TD 50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii . Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection.

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

“…Thus, it is possible to correlate the high affinity of compound 7 with the observed anti- Toxoplasma activity. The potential interaction between Tg CDPK1 protein and newly synthesized compounds could pave the way for associating these compounds’ in silico effects with the corresponding antiparasitic effect [ 29 ]. The electron-donating or electron-withdrawing substituents on the phenyl moieties as well as the steric bulkiness due to the presence of aromatic rings may play a role in the differential activity towards the parasite, as well as towards the host cells.…”

“…To set the grid boxes, re-docking of the co-crystallized ligands in each receptor was done. All the calculations were performed in triplicates and Megazol was used as a reference drug (thiadiazole antiparasitic drug) [ 29 ].…”

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

“…T. gondii seropositive rst-episode patients with schizophrenia were treated with artemether (Wang et al 2014). It has been demonstrated artemisinin and derivatives had great inhibition of the growth of T. gondii in broblasts (Molina et al 2021).…”

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…The group of (4-oxothiazolidin-5ylidene)acetic acid derivatives (99)(100)(101) showed activity against T. gondii with IC50 values of 0.46, 0.20 and 0.66 µM, respectively. In addition, besides the anti-T. gondii activity, Compounds 99-101 had also lower toxicity towards the host cells (TD50 = 60, 206, 125 µM, correspondingly) [109]. The inhibition constant (Kd) of LmPTR1 was determined by ThermoFluor ® assays.…”