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Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening

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Abstract

We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium (TsCu/Zn–SOD), a human parasite. Conformers from LeadQuest® database of drug-like compounds were selected and then docked on the surface of TsCu/Zn–SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed μM inhibitory activity toward TsCu/Zn–SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.

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Acknowledgments

This work was partially suported by Consejo Nacional de Ciencia y Tecnología-México (CONACyT, 105532, 80134-M, ECOS M05-501) and the Dirección General de Asuntos del Personal Académico (DEGAPA, IN 207507-3). P.G.-G. and R.P.-U. also thank CONACyT for graduate studies grants.

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Authors and Affiliations

  1. Área de Biofisicoquímica, Departamento de Química, Universidad Autónoma Metropolitana–Iztapalapa, 09340, México, D.F., México

    P. García-Gutiérrez & A. Rojo-Domínguez

  2. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, México, D.F., México

    A. Landa-Piedra & R. Parra-Unda

  3. Departamento de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, 04510, México, D.F., México

    A. Rodríguez-Romero

  4. Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana–Cuajimalpa, Pedro A. de los Santos 84, Col. San Miguel Chapultepec, 01120, México, D.F., México

    A. Rojo-Domínguez

Authors
  1. P. García-Gutiérrez
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  2. A. Landa-Piedra
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  3. A. Rodríguez-Romero
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  4. R. Parra-Unda
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  5. A. Rojo-Domínguez
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Corresponding author

Correspondence to A. Rojo-Domínguez.

Electronic supplementary material

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10822_2011_9498_MOESM1_ESM.doc

Supplementary Material Available: 2D structures and LeadQuest® ID for all the fifty experimentally tested compounds with high docking score predicted as inhibitors for TsCu/Zn–SOD. 2D structures and LeadQuest® ID for the twenty experimentally tested compounds with low docking scores used as negative control. Schemes for ligand-interactions of active compounds in site 1 in the optimized pose with lowest binding energy. List of residues that constituted the potential binding sites for docking on the surface of TsCu/Zn–SOD identified with Site_Finder–MOE and CASTp. Interaction energies and docking scores before and after energy minimizations for fifty experimentally tested compounds. Comparison between Dock–MOE and AutoDock–Vina docking scores for compounds 1–6 against TsCu/Zn-SOD enzyme. (DOC 1382 kb)

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García-Gutiérrez, P., Landa-Piedra, A., Rodríguez-Romero, A. et al. Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening. J Comput Aided Mol Des 25, 1135–1145 (2011). https://doi.org/10.1007/s10822-011-9498-x

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  • DOI: https://doi.org/10.1007/s10822-011-9498-x

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