Off White Middle School Matrix Metalloproteinase Inhibitors And Metal Ions On The Inhibition Of Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) are Zn²⁺-dependent endopeptidases family, which are capable of collectively degrading all kinds of extracellular matrix proteins. MMPs involved in a series of pathological and physiological processes including apoptosis, morphogenesis, proliferation and upgrowth. It seems that matrix metalloroteinase inhibitors have broad potentials in curing many important diseases including cancer, cardiovascular disease, arthritis, eye disease, immune system diseases, gynecological diseases and skin diseases. It is attractive that screening of compounds against MMPs from the natural plant extracts and developing them to some new drugs. In this dissertation, with MMPs as the target, by using the polygona-polysaccharosel, macroporous resin separation and enzymologic techniques, the active ingredients of Aconitum coreanum to MMP-16 were tracked and separated. The structure of active compound was identified, and its antibacterial activity were also explored. The inhibitory activity of trivalent, divalent and one valence metal ions and and rare earth metal ions to MMPs and bacteria was also studied.The main contents of this study include:In this dissertation, the research work in domestic and international studies on Aconitum coreanum, matrix metalloproteinase, matrix metalloproteinase inhibitors and metal ions wasreviewed.The monomer which can inhibit MMP-16 was isolated from Aconitum coreanum firstly,the experiment results show that the monomer was the main MMP-16 inhibitor in the Aconitum coreanum. The monomer was identified by IR, elemental analysis and atomic emission, the results suggested that it was dodecahydrate ammonium aluminum sulfate (NH₄Al(SO₄)₂·12H₂O). The compounds (or complex salt) containing NH₄⁺, Al³⁺, SO₄^2- were selected to study their inhibitory activity to MMP-16, the result suggested that the active group of NH₄Al(SO₄)₂·12H₂O to MMP-16 was Al³⁺. Further studies have shown that the monomer also had strong inhibitory activity(IC₅₀ less than 10μmol/L) to other MMPs (such as MMP-2,MMP-9,MMP-13,MMP-3) and its effect to cell morphology showed that it had inhibitory activity to the invasion of cancer. Therefore the monomer has the possibility to be anti-cancer drugs. The inhibitory activity of Aconitum coreanum extract and active monomer to several bacteria were also studied. The result showed that the main active monomer of Aconitum coreanum was NH₄Al(SO₄)₂·12H₂O also, and its active group was Al³⁺. The inhibitory activity of some metal ions to MMP-16 was studied. The result showed that trivalent metal ions and rare earth metal ions had inhibitory activity to MMP-16 and divalent, one valence metal ions had no activity. The inhibitory activity of the rare earth metal ions to MMP-16 showed a certain degree of regularity, that was, in the group of LREEs, MREEs and HREEs, their inhibitory activity to MMP-16 decreased with the increase in the atomic number increaseing. At the same time, the inhibitory activity of some metal ions to bacteria was studied and the result showed that not only trivalent metal ion (including rare earth metal ions) had inhibitory activity to bacteria but also divalent and a divalent metal ions had a certain extent inhibitory activity to bacteria.