Bioactivities Of Transition Metal Complexes With Novel Bacillamide Ligands Containing Pyridine Terminal Groups

Bacillamide ligands containing pyridine terminal groups is a kind of important natural products, has extensive pharmacological effects, especially in the case of antibacterial and anticancer activities, which provides the ideal guide structure for the development of new drug designing. In recent years, bacillamide containing pyridine terminal groups was one of the most studied compound, which containing multiple coordination sites, and form stable clathrate with different transition metal complex.However, the reports about the activity of such coordination compounds are rare. In order to further explore the antibacterial and anticancer activities of such bacillamide compounds.The structural modification and skeleton analysis of several existing active alkaloid compositions in seaweed and floating bacterias were taken, three bacillamide containing pyridine terminal groups were synthesized:N-Pyridin-2-ylmethylene-N’-(4-pyridin-2-yl-thiazol-2-yl)-hydrazine(L1),N-Pyridin-3-ylmethylene-N’-(4-pyridin-3-yl-thiazol-2-yl)-hydrazine(L2),N-Pyridin-4-ylmethylene-N’-(4-pyridin-4-yl-thiazol-2-yl)-hydrazine(L3).On one hand, the different space conformation characteristics formed by different pyridine replacing agents and transition metal compounds was studied; On the other hand,the antibacterial and anticancer activities of the ligands and complexes was researched.In this thesis, the work was done in two parts:First, structure study; Pyridinaldehyde, ketone of pyridine, thiosemicarbazide were taken as the raw materials, and three bacillamides containing pyridine terminal groups(L1-L3) were synthesized, which were coordinated with different transition metal salts; The monocrystallines of coordination complexes were prepared. The structure of thesynthesized compounds and complexes were characterized by MS, IR, NMR(H spectroscopy), elemental analysis, X-crystal diffraction. The fluorescence properties of the ligands and complexes were studied.Second, activities research; The antibacterial, anticancer activities of the bacillamides containing pyridine terminal groups(L1-L3) and their complexes were measured and the law of their germicidal, antibacterial, anticancer activities was summarized. At the same time, we discussed the antibacterial and anticancer activities of complexes of such compounds to different bacteria and cancer cells in vitro. These conclusions provide very important experiment basis for the development and promotion of bacillamides containing pyridine terminal groups and their metal complexes in the field of biological medicine.The main results of this thesis are as follows:1. Bacillamides containing pyridine terminal groups(L1 to L3) have good coordination performance, supramolecular complexes of different dimensions can be obtained by transition metal coordinations.2. Compounds L1 to L3 have weak fluorescence performance(slit width of 10 nm,strength of 25-80), but the fluorescence performance has greatly improved only when its coordinated with metal zinc salt; However, the compounds of cadmium, nickel, copper,manganese metal complexes show a different fluorescence change law of fluorescent efficiency, slightly increase or decline.3. The bacillamides containing pyridine terminal groups(L1, L2, L3) show different biological activity for a different pyridine replace; the complexes with different metal salts present a different pattern on the biological activity.In general, Ligand L1 and its metal complexes have high antibacterial activity, for it can basically achieve the whole level of suppression to a variety of pathogenic bacteria;ligand L2, L3 and their metal complexes have stronger inhibition to individual strains, and the inhibitory effects are not obvious to others.The antibacterial activity of compounds L1 were significantly improved after chelating with metal complexes, which illustrated the addition of transition metal have enhanced activity.The antibacterial activity of zinc metal complexes is significantly higher than other metal complexes; Moreover, nickel salts, manganese salts, which have certain toxicities,show declining activity after complexation, which provide certain reference value for heavy metal antidote for such bacillamide compounds.4. Similar to the law of antibacterial activity, the antiproliferative activity of zinc salt complexes of ligand L1 is several times higher than the corresponding ligand to four kinds of cancer cells, but after reacting with zinc salt complex, the coordination compounds appear the same or lower anticancer activity compare to the ligands, which may be related to different coordination models.