Design and molecular docking studies of biuret derivatives as potentialMatrix Metalloproteinases ۹(MMP۹) inhibitors

Introduction MMP-۹ is an important and essential protease from the large family of matrix metalloproteinases (MMPs), which belong to the category of endopeptidases dependent on zinc metal. MMP-۹ has diverse functions. It is a key role in pathophysiology, as well as an important role in cleaving extracellular matrix components . In addition, MMP۹ has significant effects on various cellular pathways, including migration, invasion, angiogenesis and metastasis of cancer cells. Dysregulation of expression or overactivation of this enzyme is associated with many pathogenesis conditions such as neurological diseases, cardiovascular diseases and especially cancer. Therefore, it is considered as an attractive target for the drug design . In recent years, the application of computer aided drug design has been increasing significantly due to advantages such as reducing costs, increasing the speed of operation and high accuracy . In connection with our interest in the synthesis of biuret derivatives , and advantages of computational chemistry, MMP۹ inhibitory activity of ۱۸ biuret derivatives was investigated by molecular docking studies, and the best compounds were selected to evaluate the enzymatic assay. Method At first, swiss target prediction server was applied to identify proposed therapeutic goal for biuret derivatives. Afterward, the Crystal structure of MMP۹, with the PDB ID of ۴XCT and resolution of ۱.۳ Aº was obtained from Protein Data Bank (www.rcsb.org). Eventually, molecular docking studies was carried out and compounds with best docking score have been selected for synthesis and enzymatic assay. Results and Discussion According to the molecular docking studies data, the binding energy and main interactions between the biuret derivatives and MMP۹ active site were precisely investigated. Based on docking score ۴ biuret derivatives were selected. These compounds can be considered as a proper candidate in order to develop new MMP۹ inhibitors.

کلیدواژه ها:

Molecular docking studies ، Matrix metalloproteinases ۹ ، Inhibitor ، Biuret derivatives