Quantitative Structure-Activity Relationship Studies on Matrix Metalloproteinase Inhibitors: Bicyclic Heteroaryl Hydroxamic Acid Analogs

A quantitative structure-activity relationship (QSAR) study has been made on some bicyclic heteroaryl hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The inhibition potencies of compounds against a number of MMPs were subjected to QSAR analysis and it was found surprisingly that the most crucial property of the molecules controlling the drug action, the hydrophobicity, to be playing a negative role here in most of the cases vis-a-vis the polarizability of the molecules is shown to be conducive to the potency. Based on this, it is proposed that the active sites in most of the MMPs might be having electronic nature and, only in a few, there may be some hydrophobic sites.