Comparison of AM1 and B3LYP-DFT for inhibition of MAO-A by phenylisopropylamines: A QSAR study

The aim of this study is to provide an initial indication regarding the scope and limitations of some state-of-the-art methods in computational chemistry, including semiempirical (AM1) and density functional theory (B3LYP), in the flip regression procedure applied to the inhibition of phenyliso-propylamines. The results show that the models established based on the density functional theory-B3LYP are better than that based on semiempirical method (AM1). It is demonstrated that electron-rich ring systems and highest occupied molecular orbital levels tended to increase activity. In this contribution, it is shown that the orientation of nodes in their occupied a orbitals, and also the energies of these orbitals explain a further large portion of the variance in their inhibitory activity.