Synthesis And Biological Activity Of Quinoline Derivatives Schiff Base And Their Metal Complexes

In this study,six new complexes were finally synthesized using 8-hydroxy-quinoline-2-carbaldehyde o-vanillin hydrazone(L1),8-hydroxy-quinoline-2-carbaldehyde salicylate hydrazone(L2)coordinated with Ln(?)rare earth metal respectively.Meanwhile,quinoline derivatives Schiff base(L3-L9)were obtained by condensation of quinoline-8-formaldehyde with methylamine,ethylamine,n-butylamine,octylamine,dodecylamine,hexadecylamine and octadecylamine,and ten novel quinoline derivatives Schiff base copper complexes were synthesized with copper metal salt using solvothermal method,subsequently.All complexes were characterized by infrared spectroscopy,mass spectrometry,elemental analysis and X-ray single crystal diffraction.The interaction between metal complexes and BSA/DNA was studied by ultraviolet absorption spectroscopy and fluorescence spectroscopy.Finally,the anti-tumor activity of all complexes in vitro were measured using the MTT method and the anti-tumor mechanism was preliminary explored.The main contents are as follows:1.Summarize the research status of non-platinum metal complex anti-tumor drugs,introduce the latest research progress of Schiff base metal complexes of quinoline derivatives.Basing on these results,the study significance and basis have been provided.2.Synthesis of quinoline derivatives Schiff bases and their metal complexes.Two acyl hydrazone Schiff base ligands,8-hydroxy-quinoline-2-carbaldehyde o-vanillin acylhydrazone(L1)and 8-hydroxyquinoline-2-carbaldehyde salicylic acid acylhydrazone(L2),were synthesized by condensation of 8-hydroxyquinoline-2-carboxaldehyde with o-vanillin hydrazine and salicylic acid hydrazine,two binuclear rare earth metal complexes and four heteromorphic rare earth complexes(1-6)were synthesized by solvothermal reaction with Gd,Dy,Er,Eu.A series of quinoline derivatives Schiff base ligands(L3-L9)were synthesized by Quinoline-8-formaldehyde with linear amine,such as Methylamine Methylamine,Ethylamine,Butylamine,Octylamine,Dodecylamine,Hexadecylamine,Octadecylamine,ten novel Schiff base copper complexes(7-16)with quinoline derivatives were synthesized by solvothermal reaction with copper metal salts.The structure was characterized by X-ray single crystal diffraction,infrared spectroscopy,mass spectrometry and elemental analysis.Complexes 1,2,10,15,and 16 have a dual-core structure,complexes 3-6 have a quad-core structure,and the remaining seven complexes have a single-core structure.All complexes as follows:Their stability was studied by ultraviolet-visible spectroscopy.3.Study on the interaction of Schiff base metal complexes of quinoline derivatives with BSA and DNA.The interaction of metal complexes with BSA and DNA was studied by ultraviolet absorption spectroscopy and fluorescence spectroscopy,and the mechanism is preliminary explored.The results show that the fluorescence of BSA is quenched by the metal complexes,and it also interacts with CT-DNA by insertion.4.Preliminary study on the antitumor activity and mechanism of quinoline derivatives Schiff metal complexes.The results are shown as follows:?.Most of the metal complexes showed higher antitumor activity than the ligands on T-24,Hep-G2,HeLa,MGC80-3,A549 and human normal embryonic lung WI-38 cells.8-Hydroxy-quinoline schiff base complex 3 shows a high inhibitory effect on human bladder cancer cell T-24;The complex 16 in quinoline-8-formaldehyde schiff base showed a high inhibitory effect on 4 kinds of tumor cells(T-24,HeLa,MGC80-3,A549),with IC50 values below 10 ?M.?.Complex 3 can induce cell cycle arrest in S phase of T-24 and HeLa cells.Complex 16 can induce cell cycle arrest in G2 phase of T-24 and HeLa cells.?.The distribution of the complex in the cell was detected by ICP-MS,and it was found that the complex could aggregate in the mitochondria and disrupt the mitochondrial function.The effects of complexes 3 and 16 on apoptosis of tumor cells were studied by Annexin?-FITC/PI double staining,ROS release and JC-1 change of mitochondrial membrane potential.The results showed that complexes 3 and 16 could induce the early apoptosis of T-24 and HeLa,and the decrease of mitochondrial membrane potential and the increase of ROS concentration,which leads to apoptosis.