Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds

Rodrigo Aguayo-Ortiz, Jaime Pérez-Villanueva, Alicia Hernández-Campos, Rafael Castillo, Nathalie Meurice, José L. Medina-Franco

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)281-294
Number of pages14
JournalFuture Medicinal Chemistry
Issue number3
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery


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