Molecular Modeling of the Toxoplasma Gondii Adenosine Kinase Inhibitors

Computer-assisted approaches might be seen as a bridge to novel medication discoveries. In 2014, the World Health Organization declared antibiotic resistance in microorganisms as a major global threat where simple diseases that were formerly manageable have now become deadly infections. Microbial resistance is a form of drug resistance where a microorganism may live even in the presence of antibiotics. Toxoplasmosis is a major worldwide parasitic infection caused by Toxoplasma gondii. Since Toxoplasma gondii is not capable of purine synthesis, the protein adenosine kinase (EC.2.7.1.20) is an important enzyme in its life pathway. Therefore, Toxoplasma gondii adenosine kinase has recently been considered a target for developing anti-Toxoplasma agents. This study aimed to develop a 3D QSAR model to predict the activity of adenosine kinase inhibitors in Toxoplasma gondii and to find new potent inhibitors. The acceptable values of 0.98, 0.83, and 0.91 were observed for the goodness of fit (R2), internal cross-validation (Q2), and external cross-validation (R2pred) indices, respectively. The robustness of the model was confirmed by applying the Y-scrambling analysis, and values of ~ 0.18 and ~ 0.0025 were observed for R2intercept and Q2intercept, respectively. This confirmed that indices calculated for the original model were not based on the chance correlation between independent and dependent variables. New ligands were then proposed based on the structural virtual screening using the SwissSimilarity web tool and the ZINC database. The SwissADME web tool was used to predict the pharmacokinetic properties of the new compounds, and a promising compound was suggested for further research.