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 journalArticle

11 Citations (Scopus)

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. 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
Volume6
Issue number3
DOIs
StatePublished - 2014

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Trichomonas vaginalis
Giardia lamblia
Structure-Activity Relationship
Benzimidazoles
Parasitic Diseases
Parasites
benzimidazole

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

Cite this

Aguayo-Ortiz, R., Pérez-Villanueva, J., Hernández-Campos, A., Castillo, R., Meurice, N., & Medina-Franco, J. L. (2014). Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds. Future Medicinal Chemistry, 6(3), 281-294. https://doi.org/10.4155/fmc.13.173

Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds. / Aguayo-Ortiz, Rodrigo; Pérez-Villanueva, Jaime; Hernández-Campos, Alicia; Castillo, Rafael; Meurice, Nathalie; Medina-Franco, José L.

In: Future Medicinal Chemistry, Vol. 6, No. 3, 2014, p. 281-294.

Research output: Contribution to journalArticle

Aguayo-Ortiz, R, Pérez-Villanueva, J, Hernández-Campos, A, Castillo, R, Meurice, N & Medina-Franco, JL 2014, 'Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds', Future Medicinal Chemistry, vol. 6, no. 3, pp. 281-294. https://doi.org/10.4155/fmc.13.173
Aguayo-Ortiz R, Pérez-Villanueva J, Hernández-Campos A, Castillo R, Meurice N, Medina-Franco JL. Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds. Future Medicinal Chemistry. 2014;6(3):281-294. https://doi.org/10.4155/fmc.13.173
Aguayo-Ortiz, Rodrigo ; Pérez-Villanueva, Jaime ; Hernández-Campos, Alicia ; Castillo, Rafael ; Meurice, Nathalie ; Medina-Franco, José L. / Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds. In: Future Medicinal Chemistry. 2014 ; Vol. 6, No. 3. pp. 281-294.
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