title: 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.
authors.affiliation: Área de Biofisicoquímica, Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, 09340, México, D.F., México. pgarcia@ciencias.unam.mx
authors.forename: P
authors.initials: P
authors.lastname: García-Gutiérrez
authors.forename: A
authors.initials: A
authors.lastname: Landa-Piedra
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Romero
authors.forename: R
authors.initials: R
authors.lastname: Parra-Unda
authors.forename: A
authors.initials: A
authors.lastname: Rojo-Domínguez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D041201:Taenia solium / Q000187:drug effects / Q000201:enzymology*; D013622:Taeniasis / Q000188:drug therapy
chemical_list: D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D013482:Superoxide Dismutase