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

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.

Estructura del gen para la superóxico dismutasa de CU/ZN de Taenia solium y el análisis de su región promotora

“…Además de los resultados obtenidos en este proyecto, es importante resaltar el de nuestras colaboraciones, en donde una vez obtenida la estructura cristalográfica con apoyo del grupo de la Dra. Adela Rodríguez en el instituto de química de la UNAM [9], se realizaron análisis de docking en colaboración del Dr. Arturo Rojo en la UAM Iztapalapa [52]. De acuerdo a nuestros resultados, la búsqueda de fármacos se enfocó en compuestos que se unen a las diferencias que existen entre la SOD de Homo sapiens y la de T. solium.…”