Self-organizing molecular field analysis on human β-secretase nonpeptide inhibitors: 5, 5-disubstituted aminohydantoins

Abstract

5, 5-disubstituted aminohydantoins have been recently reported as potent and selective human β-secretase (BACE-1) inhibitors. Self-Organizing Molecular Field Analysis (SOMFA) is used to study the correlation between the molecular properties and biological activities of the 5, 5-disubstituted aminohydantoins inhibitors. Four different alignments and two charge-assigning methods were investigated. The model derived from the superposition of docked conformation with AM1 charge showed satisfied predictive ability, which has good non-cross-validated r2 (0.842), cross-validated q2 (0.792), F-test value (254.75) and satisfied predictive ability r2pred (0.721). Analysis of SOMFA model may provide some useful information in the design of BACE-1 inhibitors with better spectrum of activity.