Synthesis And Biological Activity Of Benzoxazine Ketone Chalcone Compounds And Thiazole-pyrazoline Compounds

The compounds of chalcone are core structure unit of the natural and synthetic drugs, which belongs to a class of flavonoids and is formed by α,β-unsaturated carbonyl group attached to two aromatic rings. Because chalcones are low toxicity, high efficiency, and can be further modified to give other compounds, they play a very important role in drug discovery, such as anti-inflammatory, antibacterial, anti-parasitic, acetylcholine inhibitors, treatment of dyslipidemia and so on. Meanwhile, in the light-emitting materials and agriculture also has a wide range of uses, such as making pesticides, herbicides, luminescent materials. Scientists have conducted extensive research in the anti-cancer activity of chalcones. They modified the structure of chalcones and tested anticancer activity of chalcones, meanwhile studied further mechanism.Chalcone compounds can be further modified to get pyrazoline compounds. Because pyrazoline is simple structure, easy of synthesis, and more importantly, its structure can be further modified to get different compounds with different substituents at different sites of a five-membered ring structure, so these compounds play a very important role in medicine, pesticide research. In medicine, pyrazoline compounds have used for anti-bacterial, anti-inflammatory, anti-cancer, anti-viral, treatment of diarrhea, treatment of HIV and other effects. In addition, they also have a wide range of uses in the materials and agricultural activity.The purpose of this thesis is to synthesize and evaluate the biological activity of modified chalcone compounds by introducing benzoxazinone basic structure and further for screening molecules with potential anticancer activity. It also determined the crystal structure of a representative benzoxazine ketones chalcone compound. In addition, we also synthesized a series of pyrazoline compounds, their biological activity is expected to be measured.The thesis consists of two parts: 1. Synthesis and biological activity of benzoxazine ketone chalcone compounds1.1Under alkaline conditions, acetylbenzimidazole oxazinone compounds reacted with aldehydes got some out chalcone compounds, the products were characterized by1H NMR,13C NMR, IR and HRMS, and the crystal structure was determined.1.2On the basis of synthetic chalcone series of compounds, their biological activities were determined. Preliminary biological results showed that compound3a-3d could inhibit the lung cancer of A549cells, further research found that compounds inhibit the biological aspects of cancer cells by inducing autophagy lung cancer cells and inhibiting of cell cycle to inhibit cell proliferation.2. The synthesis and characterization of thiazole-pyrazoline compoundsBased pyrazoline derivatives have good biological activity, generally have fluorescent properties, as well as the advantages of thiazole compounds, we designed and synthesized thiazole-pyrazoline compounds. We first synthesized thioamides pyrazoline, then reacted with2-bromo-1-(pyridin-4-yl)ethanone hydrobromide in ethanol as a solvent for further reaction to give a new compounds. The structure of the compound was characterized by1H NMR and HRMS. These compouns are expected to further bioassay.In conclusion, we synthesized a number of new chalcone compounds, and evaluated the biological activity of this series of compounds. We found that they had good biological activity and had a certain effect on the inhibition of A549cancer cells. Furthermore, the mechanism was studied and found that the compounds can induce autophagy of cancer cells. The results provided the foundation to explore the structure activity relationship. We also designed and synthesized thiazole-pyrazoline compounds in higher yield by the simple post-processing and these compounds can be used as pH probes. The biological activities of these compounds are evaluating.