2D-QSAR Studies on the Norcantharidin Analogues as Protein Phosphatase 1 and 2A Inhibitors

The Two-dimensional Quantitative Structure-activity Relationship (2D-QSAR) of a series of novel norcantharidin analogues, which exhibit inhibitory activities of protein phosphatase 1 and 2A (PP1 and PP2A), has been studied with a combined method of ab initio (HF), molecular mechanics (MM+) and statistics. The established 2D-QSAR model (Eq. 1) for PP1 shows a reasonable regressive performance (R-2 = 0.749), and the hydrophobic property of this molecule plays a decisive role in determining the inhibitory activity of PP1. In addition, the established 2D-QSAR model (Eq. 2) for PP2A also shows an acceptable regressive performance (R-2 = 0.701), and the dipole moment of the molecule determines the inhibitory activity of PP2A.