A Quantitative Structure-Activity Relationship Study of Caffeic Acid Amides as Selective Inhibitors of Matrix Metalloproteinase

Introduction Matrix metalloproteinases (MMPs) represent a family of zinc dependent endopeptidases which is involved in the breakdown of components of the extracellular matrix and helps in tissue remodeling [1]. The process is vital in embryonic development, pregnancy, growth and wound healing. Usually the activity of MMPs is restricted by the equilibrium between synthesis of active MMPs and the presence of endogenous inhibitors, namely the tissue inhibitor of metalloproteinases (TIMPs) [1]. During tumor progression this equilibrium is disturbed and the increased level of certain MMPs is thought to be involved in metastatic tumor dispersion and angiogenesis leading to a malignant phenotype [2,3]. The zinc dependent endopeptidases are then secreted as inactive zymogens in the extracellular matrix by the tumor cells or by neighboring stromal cells close to tumor cells. The MMP-2 (gelatinase A) and MMP-9 (gelatinase B) appear to play significant role in these progressions, considering that they are engaged in metastatic tumor dispersion and angiogenesis [4,5].