Studies On Synthesis And Antibacterial Activities Of Ligustrazine’ Derivatives

The Chuan Xiong of traditional Chinese medicine is known as “Blood and discharge of the medicine”. Ligustrazine（tetramethylpyrazine） as its active ingredient is used to cure the coronary heart disease and ischemic cerebrovascular disease. Because of fast metabolism and short half-life, the ligustrzine must be continually dosed and is easy to cause the cumulative intoxication yet. The application of ligustrazine is limited. In order to explore the potential medicinal value in antibacterial agents, anti-cancer drugs and other aspects, we reform and modify the structure of ligustrazine to get 2-acetylpyrazine compounds and their transition metal complexes and the antimicrobial activities of them were tested to get antibacterial drugs with high efficiency, low toxicity and well structure-activity, which provides very important foundation for the compounds containing acetylpyrazine group in application of the pharmaceutical industry.The main work in this paper was listed as fellows:1. Using 2-acetylpyrazine as raw material, a series of acetylpyrazine derivatives were synthesized as follows:（E）-1-（pyrazin-2-yl）-3-（pyridin-3-yl）prop-2-en-1-one（L1）（E）-N’-（1-（pyrazin-2-yl）ethylidene） isonicotinohydrazide（L2）（E）-N’-（1-（pyrazin-2-yl）ethylidene） nicotinohydrazide（L3）2. The structure of ligands such as L1, L2 and L3 were characterized by IR, NMR and MS.3. Using L1, L2 and L3 as ligands, a series of transition metal complexes were synthesized.The crystal structure of [Ag（L2）NO₃] and [Cd（L2）Ac2] were characterized by X-ray single crystal diffraction and their different spatial conformation was studied.4. The fluorescence property of L1, L2 and L3 and their transition metal complexes were tested. The complexes were composed of [Ag（L1）NO₃], [Ag（L1）Cl O4], [Ag（L2）NO₃],[Ag（L2）Cl O4], [Zn（L2）SiF₆], [Zn（L2）（BF4）₂], [Ag（L3）NO₃], [Zn（L3）（BF4）₂], [Zn（L3）SiF₆][Zn（L3）（CF₃SO₃）₂].5. The biological activities of ligands such as L1, L2, L3 and their 15 kinds of transition metal complexes were studied. The regularity of disinfection and antibacterial effect were summarized.The results were listed as follow:1. From the results, it can be got that the L1, L2, L3 and their 15 kinds of transition metal complexes have different degree inhibitory effects on selected seven representative strains（Escherichia coli, Staphylococcus albus, Salmonella, Sarcina luteus, Bbacillus subtilis,Staphylococcus aureus, Bacillus cereus）. The ligand L1 has well effect on Staphylococcus albus and Salmonella; the bactericidal effect of ligand L3 is relatively strong compared to the ligand L2, especially for Staphylococcus aureus and Bacillus cereus, revealing the best bactericidal effect; the introduction of metal ions changes the biological activities of such kinds of ligands and provides informative choice to look for the new antibacterial drugs.2. The crystal structures of complexes [Ag（L2）NO₃] and [Cd（L2）Ac2] are new. The[Ag（L2）NO₃] is formed by triclinic crystal system and the coordinated model is ML2. The[Cd（L2）Ac2] is formed by monoclinic crystal system and the coordinated model is M3L2.3. By comparing the fluorescent properties of ligands and complexes, we know that the introduction of the metal ions changes fluorescence intensity of such kinds of ligands and the complexes are synthesized by the ligands and metal ions.