| Thiosemicarbazone compounds due to good biological activity have been attracted people’s attention.In antitumor activities the transition metal complexes of thiosemicarbazone increase the efficacy of these compounds than the ligand alone.In this paper,the Schiff base ligands of 2-thiophene formaldehyde and isopropyl-2-pyridone with four different amino thiourea synthesized eight kinds of Schiff base metal complexes were studied.The main research contents are as follows.1.The research on the status quo and anti tumor;Cu as the research progress of anti-tumor drugs in metal,status quo of the progress of biological activity of Schiff bases and their metal complexes,and elaborates the contents and research significance of this paper.2.By MTT method,found four different 2-thiophene thiosemicarbazone formaldehyde condensates 2-thienyldehyde thiosemicarbazone(L1);2-thienyldehyde-4-methyl thiosemicarbazone(L2),2-thienyldehyde-4-phenyl thiosemicarbazone(L3),2-thienyldehyde-4,4-2-ethyl thiosemicarbazone(L4)and Four different isopropyl-2-pyridoneketoneaminothiourea condensates:isopropyl-2-pyridone ketone thiosemicarbazone(L5),Isopropyl-2-pyridine ketone-4-methyl-3-thiosemicarbazone(L6),Isopropyl-2-pyridine ketone-4-phenyl-3-thiosemicarbazone(L7),isopropyl-2-pyridineketone N,N-2-methyl-3-thiosemicarbazone(L8)have the different proliferation inhibition of 6 kinds of human tumor cell lines T-24,NCI-H460,A549,Hep-G2,HeLa,MGC-803 and human normal liver cell line HL-7702 in vitro.The metal complexes of Cu[Cu3(L1)6Br3](1),[Cu2(L2)4Br2](2),[Cu4(L3)4](3),[Cu(L4)2](4),[Cu(L5)Cl](5),[Cu(L6)Cl](C2H3N)(6),[Cu(L7)Cl](7),[Cu(L8)Cl](8)also have different activities.The results showed that all the complexes had higher antitumor activity against T24 human bladder cancer cells and HeLa human cervical cancer cells,and the anticancer activity of the corresponding metal complexes was much higher than that of the ligand.3.On the basis of MTT experiment,two kinds of complexes with better activity,complex 1 and complex 8 as the representative were studied,determined by the induction of human bladder cancer T-24 cells cycle arrest by flow cytometry.The experimental results showed that the complexes 1 and 8 complexes with T-24 cells in vitro and apoptosis were induced by tumor cells,and the apoptosis rate and the concentration was positively related to the use of drugs.Cell cycle detection by flow cytometry,the experimental results showed that the complexes of 1 arrested T-24 cells in G2/M phase,the complex 8 were blocked T-24 cells in S phase.Flow cytometry(FCM)was used to detect JC-1.The results showed that the complexes 1 and 8 decreased the mitochondrial membrane potential of T-24 cells and induced the apoptosis of T-24 cells.With the increase of drug concentration,the induction effect was more obvious.4.The Western Blot experiment found that complexes 1 and 8 can make T-24 cells Bax,Cyt C,Caspase-3,Caspase-9 expression was significantly increased,anti apoptosis protein Bcl-2,reduce the expression of Bcl-xl was significantly increased the expression of Caspase-9 activated Caspase-3 that complexes 1 and 8 through the mitochondrial apoptotic pathway to induce T-24 cells apoptosis.Cell cycle regulation,complexes 1 and 8 E2F-1,Cyclin A and Cyclin E expression increased at the same time,the expression of Cdk 2 and Cdk 4 decreased.5.The gel electrophoresis experiment of DNA and TopI;TopI can make the PBR322 state of DNA in the state of super helix spiral,and then turn into a relaxed state,complex 1 and 8 can inhibit the activity of Top I,and with the increase of drug concentration,the inhibitory effect is more obvious. |
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