Future medicinal chemistry · 2013
Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Aguayo-Ortiz Rodrigo, Pérez-Villanueva Jaime, Hernández-Campos Alicia, Castillo Rafael, Meurice Nathalie, Medina-Franco José L
Аннотация
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.
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.