QSAR and validation analysis on MMP-13 inhibitors

Abstract

Matrix metalloproteinases (MMPs) play an important role in the tissue modeling and remodeling of the extracellular matrix. Abnormal activity of these enzymes was associated with metastasis, angiogenesis, cardiovascular disease, osteoarthritis, and rheumatoid arthritis. Multiple regression procedure was employed to perform QSAR (Quantitative Structure Activity Relationship) analysis on a set of 72 α-sulfone hydroxamate MMP-13 inhibitors. Outlying data was removed using Relative Error calculation and Extent of Extrapolation. The activity contributions of 57 compounds after removing outliers, was determined and the validation procedures such as cross-validation r2, R2ev, ext etc. were obtained. The generated model could be useful in designing more potent inhibitors of MMP-13.