Chemoinformatics: Directions Toward Combating Neglected Diseases

Indexed in: Scopus

Low-income populations in developing regions of Africa, Asia and the Americas have been particularly injured by a group of tropical infections denominated neglected diseases. Compared to important ...
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Molecular Modeling of the Toxoplasma gondii Adenosine Kinase Inhibitors

Pp. 162-173 (12)

Daiana Teixeira Mancini, Elaine F. F. da Cunha, Teodorico C. Ramalho and Matheus P. Freitas

Abstract

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

Affiliation:

Department of Chemistry, Federal University of Lavras, P.O. Box 3037, 37200-000, Lavras, MG, Brazil