2D QSAR Studies on Series of Human Beta-secretase (BACE-1) Inhibitors
Daniela Santos Cruz,
Marcelo Santos Castilho.
β-secretase (BACE-1) plays a pivotal role in the β-Amyloid plaques formation, which is responsible for progressive
cognitive and memory loss commonly found in Alzheimer disease patients. As a consequence, it has been considered
as a good target for drug development efforts. Early work focused on the synthesis of peptidomimetics, but poor
pharmacokinetics profile prevented advancing lead compounds to clinical trials. As an alternative, aminoimidazoles, aminohydantoins
and aminopyridines derivatives that inhibit BACE-1 were designed. Herein we report statistically sound descriptor-
based (r2 = 0.87, q2 = 0.85, 6 PCs) and fragment-based (r2 = 0.91, q2 = 0.84, 6 PCs) QSAR models, that show high
predictive ability (r2
pred = 0.84, averaged r2
m=0.78) and underscore polar interactions that are important for BACE-1 inhibition.
Keywords: Alzheimer, β-Amyloid, Beta-secretase (BACE-1), 2D-QSAR, Hologram QSAR.
Rights & PermissionsPrintExport