3D-QSAR modeling, pharmacophore-based virtual screening, and assessment of ADMET properties for in silico identification of potential inhibitors of Toxoplasma gondii adenosine kinase

Toxoplasma gondii is a ubiquitous obligate intracellular protozoan parasite responsible for toxoplasmosis in humans and other warm-blooded animals such as livestock, pets, and birds. This highly prevalent chronic infection affects one-third of the world population, especially in pregnant women and immunodeficient patients undergoingchemotherapy [1-2]. Toxoplasma gondii adenosine kinase (TgAK, EC.2.7.1.20) is the main path of adenosine metabolism in this parasite. This enzyme is noticeably more active compared to other enzymes of the purine salvage in T. gondii. The enzyme also can be applied as a potential chemotherapeutic target for the treatment of toxoplasmosis[3]. Despite serious morbidity and mortality caused by this parasite, due to the limited efficacy and side effects of current drugs, the design, identification, and synthesis of new compounds is still ongoing. Computer-aided drug design (CADD) can be employed to facilitate the drug discovery process by reducing time and costs [4]. Quantitativestructure-activity relationship (QSAR) modeling is the major cheminformatic approach to discover novel hits by creating a correlation between molecular information of compounds and their biological activities. Using reliable statistical models allows activity prediction of new hits before the synthesis [5].