The Synthesis Of Apple Acid Derivatives Of Matrix Metalloproteinase And Their Activities Against K562in Vitro

The matrix metalloproteinases (matrix metalloproteinase, MMPs) is a group of zinc depended on protease, and it is usually generated by fibroblasts, neutrophils, macrophages and tumor cells. It can clear away biological macromolecules such as collagen molecules, and it also can degrade collagen and proteoglycans, and provide appropriate space for new cells growing. MMPs has a broad substrate specificity, but not absolute. The same kind of MMPs can degrade components of a variety of extracellular matrix (extracellullamatrix ECM). MMPs is an indispensable enzyme in degradation of extracellular matrix. Extracellular matrix and basement membrane is the fundamental barrier to growth and spread of tumor. MMPs and its inhibitor is the main regulator for extracellular matrix metabolism. In normal steady state, MMPs in an organization rarely expresses, but its expression will be increased apprantely in other inflammatory cytokines, hormones, growth factor stimulation and cell transformation process. Tumor cells depend on to degrade extracellular matrix MMPs, so as to promote its invasion and metastasis. Therefore, MMPs has been demonstrated to play an important in tumor growth, invasion, and metastasis, and cancer tissue blood vessel growth. It is also closely related to malignant phenotype of invasive tumors and cancer patients’bad prognosis. As a result, inhibiting the activity of MMPs can effectively control the occurrence development and metastasis of tumor. Matrix metalloproteinase inhibitors (MMPIs) has become a hot topic in anticancer drug research and development in recent years.Studies show that rely on the structural features of MMPs, different types of matrix metallopr-oteinase inhibitors (MMPIs) have been designed and synthesized. MMPIs structure Characteristics:there is zinc chelating groups (such as carboxyl, hydroxamic acid, thiol, etc.)in this structure; is a group which can form hydrogen bonds with the skeleton of the enzyme; there may be more side-chain which can interact with enzyme sites by vander Waals forces. Some studies show that2-amino-benzothiazole and its derivatives have good anti-cancer activity,at the sometime it is an important intermediate of synthetic drugs,while malic acid is also an important organic acid,on the other hand malic acid can increase the stability of the body’s absorption of drugs and improve their ability. Under the guidance of above design ideas, according to the principle of activity put together,put the Benzothiazole derivatives with malic acid together.The article designed and synthesized2-amino-benzothiazole and its derivatives. Based on these theories, a series of derivatives can be synthesized by combing2-amino-benzothiazole with malic acid; these derivatives total number is16. Its chemical structure is confirmed by IR, ESI-MS and1H NMR. By screening anti-tumor activity in vitro, the experiment selects human erythrocyte leukemic K562cells to screen anti-tumor activity of the target product. In the use of tetrazolium salt colorimetric, it has been indirectly determined target product changes on tumor cell proliferation, and calculated half of its anti-tumor inhibitory concentration (IC50). Filtered out the good activity of compounds in vitro, these compounds also show good inhibitory activity in vitro. Through the experiment, several active and new structure derivatives have been screened initially. Based on the rational drug design, it is expected to have good anti-tumor activity in the body, too.