Study On Antitumor Activity And Mechanism Of Isoliquiritigenin And Dibenzoxanthenes Derivatives In Vitro

Malignancies has caused great trauma on people's physiology and psychology,the number of folks who get cancer were increased every year.Therefore,seeking new drugs and new treatments become the focus of domestic and foreign researchers.Isoliquiritigenin,the natural compounds extracted from licorice,has been shown a wide range of pharmacological activities,but their anti-tumor activity and mechanism,in vitro,need to be further explored.Dibenzoxanthenes compounds,as potential photosensitizers,will play an important role in photodynamic therapy.Firstly,the ability of dibenzoxanthenes compounds bind to CT-DNA and BSA,at the molecular level,has been investigated.And then we evaluated the anti-tumor mechanism of the new dibenzoxanthenes compounds at the cellular level.The main points of five chapters within this dissertation are summarized as follows:1.The fundamental conception of Isoliquiritigenin and dibenzoxanthenes derivatives,the anti-tumor research progress,background,contents and significance of the dissertation were summarized.2.Using isoliquiritigenin as the research object,the MTT method was used to investigate the cytotoxicity in vitro,and then we studied the anti-tumor mechanism of isoliquiritigenin through the three aspects of apoptosis,invasion and autophagy.In a certain concentration,isoliquiritigenin can effectivelyinduce apoptosis of PC-12 cells and inhibit the cell invasion.The results demonstrated that autophagy and apoptosis were into synergistic effect.3.The two new dibenzoxanthenes compounds were synthesizedusing binaphthol.Firstly,the fluorescence spectra,gel electrophoresis,UV-Vis spectra were used to investigate the binding ability and mode of the compounds to CT-DNA and BSA,and then the in vitro anticancer methods were applied to study of antitumor mechanism.The results suggested that compounds showed high cytotoxicity against BEL-7402 cells in vitro.4.The new dibenzoxanthenes compounds synthesized by the LiAl H4 reduction reaction with the metal ion Cu-catalyzed cross-coupling reaction are identical isomers.Todetect whether the compounds can be a potential photosensitizer,we utilized the related experiment to explore the photo-activity through assessing the effect of irradiation.DPBF experiments show that the compounds can produce single-phase oxygen after light excitation,and then ROS,JC-1,Western Blot and other experiments were used to study the anti-tumor mechanism of the compounds after under irradiation.5.Four new dibenzoxanthene compounds were synthesized.The photosensitivity and anti-tumor mechanism of the compounds were explored in detail.The experimental results show that the compounds also have photosensitivity and may induce the apoptosis of cell through the mitochondrial pathway.