title: Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds.
abstract: BACKGROUND
  Benzimidazole derivatives are promising compounds for the treatment of parasitic infections. The structure-activity relationships of 91 benzimidazoles with activity against Trichomonas vaginalis and Giardia intestinalis were analyzed using a novel activity landscape modeling approach.
  
  
  RESULTS
  We identified two prominent cases of 'activity switches' and 'selectivity switches' where two R group substitutions in the benzimidazole scaffold completely invert the activity and selectivity pattern for T. vaginalis and G. intestinalis.
  
  
  CONCLUSIONS
  A chemoinformatic methodology was used to rapidly identify discrete structural changes around the central scaffold that are associated with large changes in biological activity for each parasite. The structure-activity relationships for the benzimidazole derivatives is smooth for both protozoan with few but markedly important activity cliffs.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Aguayo-Ortiz
authors.forename: Jaime
authors.initials: J
authors.lastname: Pérez-Villanueva
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meurice
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D017076:Computer-Aided Design; D062313:Databases, Pharmaceutical; D015195:Drug Design; D005260:Female; D016829:Giardia lamblia / Q000187:drug effects*; D005873:Giardiasis / Q000188:drug therapy*; D006801:Humans; D013329:Structure-Activity Relationship; D014247:Trichomonas Vaginitis / Q000188:drug therapy*; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D001562:Benzimidazoles; C031000:benzimidazole