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Interaction energies of nitrofurans with trypanothione reductase and glutathione reductase studied by molecular docking
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2007 (English)In: Journal of Molecular Structure: THEOCHEM, ISSN 0166-1280, Vol. 818, no 1-3, 7-22 p.Article in journal (Refereed) Published
Abstract [en]

A theoretical docking study was conducted on a sample of previously reported nitrofuran derivatives, at the binding sites of Trypanosoma cruzi trypanothione reductase (TR) and human erythrocyte glutathione reductase (GR), in order to examine interaction energies (affinities) towards the parasite enzyme and check for selectivity with respect to the human counterpart. A large proportion of nitrofurans were previously shown to be TR inhibitors and some of them have in vitro trypanocidal action as well. The analysis of data collected from the docking procedure was undertaken both from the numeric and graphical standpoints, including the comparison of force field energies, molecular contacts and spatial location of the different orientations that ligands acquired at the binding sites. The results clearly suggest that nitrofurans are not able to selectively bind at the active site of the parasite TR, attaining even larger interaction energies at GR active site. The reason for inhibitor specificity is two-fold: (a) the nitrofuran group acts as a strong electrostatic anchor in GR; (b) the compounds form more stable complexes when binding at the non-selective dimmer interface. Therefore, these two aspects should be specially considered when seeking good candidates for leaders in regards the development of drugs with selective inhibition of TR.

Place, publisher, year, edition, pages
2007. Vol. 818, no 1-3, 7-22 p.
Keyword [en]
Nitrofurans, Trypanothione reductase, Binding affinity;, Docking, Chagas’ disease
National Category
Chemical Sciences
URN: urn:nbn:se:uu:diva-11295DOI: 10.1016/j.theochem.2007.04.035ISI: 000249706700002OAI: oai:DiVA.org:uu-11295DiVA: diva2:39063
Available from: 2007-08-27 Created: 2007-08-27 Last updated: 2011-01-25Bibliographically approved

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