Thiazolidinone derivatives show inhibitory activity (IC50) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index . To disclose the target proteins of the thiazolidinone core in this parasite, researchers explored in silico the active sites of different T. gondii proteins.

Researchers estimated thiazolidinone molecules with an inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core

Toxoplasma gondi is the parasite that infects a large variety of mammals – including humans – and represents a significant public health concern. T. gondii belongs to the species Apicomplexan and is distributed globally.

It is estimated that about one-third of the world's population is infected. The infection is usually asymptomatic in immunocompetent individuals, although some studies report that chronic infection may be associated with changes in behavior and other physiological processes, such as schizophrenia and suicide .

The researchers have considered possible molecular-targets for thiazolidinone derivatives in T. gondii and explored the mechanism of action of these compounds through in silico experiments. We chose proteins that play essential roles in the survival and virulence of T. gondii.

Women who acquire the infection during pregnancy transmit the parasite to the fetus by congenital infection , affecting its development, which can be lethal in immune compromised individuals.

The targets chosen were: the small subunit of ribonucleotide reductase (TgRNR2), protein disulfide isomerase (TgPDI), ROP18 kinase protein (TgROP18), and calcium-dependent protein kinase 1 (TgCDPK1).

Protein-ligand interaction

The results of the study are based on the results of the study. and Carradori et al. Finally, we chose a promising target to further characterize its protein-ligand interactions by molecular dynamics (MD) simulations.

The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an essential factor for the virulence and survival of the parasite.

Researchers presented the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii.

Protein kinase of T. gondii

The results of the study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. 

The study findings highlight the importance of using computational studies for the understanding of the action mechanism of compounds with biological activity.