TY - JOUR
T1 - Chemoinformatic characterization of activity and selectivity switches of antiprotozoal compounds
AU - Aguayo-Ortiz, Rodrigo
AU - Pérez-Villanueva, Jaime
AU - Hernández-Campos, Alicia
AU - Castillo, Rafael
AU - Meurice, Nathalie
AU - Medina-Franco, José L.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
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U2 - 10.4155/fmc.13.173
DO - 10.4155/fmc.13.173
M3 - Article
C2 - 24279680
AN - SCOPUS:84893109925
SN - 1756-8919
VL - 6
SP - 281
EP - 294
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 3
ER -