Drug Discov Ther. 2008;2(1):52-57.

3D-QSAR study with pharmacophore-based molecular alignment of hydroxamic acid-related phosphinates that are aminopeptidase N inhibitors.

Zhu HW, Fang H, Wang L, Hu WX, Xu WF


3D-QSAR models for a series of aminopeptidase N inhibitors were developed based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA).GALAHAD, a pharmacophore generation module involving a genetic algorithm, was used to generate the pharmacophore model of the series of inhibitors. Molecules both in the training set and test set were aligned to the pharmacophore model. Values for the CoMFA model were r2 = 0.992, q2 = 0.586, SEE = 0.111, and F (8, 10) = 191.263. Values for the CoMSIA model were r2 = 0.990, q2 = 0.776, SEE = 0.123, and F (7, 11) = 156.68. This model can help not only in improving current understanding of enzyme-ligand interactions but also in predicting the activity of derivatives and designing new compounds with better potency.

KEYWORDS: Aminopeptidase N, 3D-QSAR, CoMFA, CoMSIA

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