Abstract
Toxoplasma gondii (T. gondii) is the most common cause of secondary central nervous system infection in immunocompromised persons such as AIDS patients. Dihydrofolate reductase and thymidylate synthase enzymes have been studied as attractive targets against parasitic diseases, since they are involved in cell proliferation and influence on DNA synthesis. In this paper, we propose three-dimensional structures of T. gondii dihydrofolate reductase and thymidylate synthase based on homology modeling. In addition, we assessed the interaction mode of pyrimidine analogs in the active site of T. gondii and human enzymes, in order to direct the planning of new compounds that can be used against toxoplasmosis. According to the docking studies, predicted pIC50 values for proposed compounds were higher than those of the experimentally most active compound.
Keywords: Molecular modeling, toxoplasmosis, dihydrofolate reductase and thymidylate synthase.
Current Bioactive Compounds
Title:Interactions of Pyrimidine Derivatives with Dihydrofolate Reductase and Thymidylate Synthase: Directions Toward Combating toxoplasmosis
Volume: 9 Issue: 2
Author(s): Letícia C. Assis, Letícia Santos-Garcia, Teodorico C. Ramalho and Elaine F. F. da Cunha
Affiliation:
Keywords: Molecular modeling, toxoplasmosis, dihydrofolate reductase and thymidylate synthase.
Abstract: Toxoplasma gondii (T. gondii) is the most common cause of secondary central nervous system infection in immunocompromised persons such as AIDS patients. Dihydrofolate reductase and thymidylate synthase enzymes have been studied as attractive targets against parasitic diseases, since they are involved in cell proliferation and influence on DNA synthesis. In this paper, we propose three-dimensional structures of T. gondii dihydrofolate reductase and thymidylate synthase based on homology modeling. In addition, we assessed the interaction mode of pyrimidine analogs in the active site of T. gondii and human enzymes, in order to direct the planning of new compounds that can be used against toxoplasmosis. According to the docking studies, predicted pIC50 values for proposed compounds were higher than those of the experimentally most active compound.
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Cite this article as:
Assis C. Letícia, Santos-Garcia Letícia, Ramalho C. Teodorico and Cunha F. F. da Elaine, Interactions of Pyrimidine Derivatives with Dihydrofolate Reductase and Thymidylate Synthase: Directions Toward Combating toxoplasmosis, Current Bioactive Compounds 2013; 9 (2) . https://dx.doi.org/10.2174/22115528112019990010
DOI https://dx.doi.org/10.2174/22115528112019990010 |
Print ISSN 1573-4072 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6646 |
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