Toxoplasma gondii (T. gondii) is the most common cause of secondary central nervous
system infection in immunocompromised persons such as AIDS patients. Since purine salvage is
essential for T. gondii and for other parasitic protozoa, inhibition of this salvage should block parasite
growth. T. gondii adenosine kinase (EC 2.7.1.20) is the major route of adenosine (purine nucleoside)
metabolism in this parasite. Four-Dimensional Quantitative Structure-Activity Relationship (4D-QSAR)
analysis was applied to a series of 41 inhibitors of T. gondii adenosine kinase. Optimized 4D-QSAR
models were constructed by Genetic Algorithm (GA) optimization and partial least squares (PLS)
fitting, and evaluated by the leave-one-out cross-validation method. Moreover, we have used docking
approaches to study the binding orientations and predict binding affinities of some benzyladenosines
with adenosine kinase.
Keywords: Toxoplasma gondii, adenosine kinase, docking
