Three-dimensional quantitative structure-activity relationship (CoMFA and CoMSIA) studies on galardin derivatives as...

Three-dimensional quantitative structure-activity relationship models have been derived using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and molecule docking for the training sets of galardin-based matrix metalloproteinase inhibitors (MMPIs). The statistical values for the best models are significant. The models showed that the steric effect near the S1' pocket and hydrogen-bonding effect of the zinc binding group play key roles on the inhibitory activity of gelatinase A. The sets of the training and test proved the models were stable and predictive, and may have a good prediction for the inhibition activities of galardin derivatives as gelatinase A inhibitors. The results not only lead to a better understanding of the molecular mechanisms and structural requirements of gelatinase A inhibitors but also can help to design novel inhibitors against gelatinase A.