Studies On The Synthesis And Anticancer Ability Of Metal Complexes With Schiff Base And Acylhydrazone Ligands

The discovery of cisplatin [Pt(NH3)2Cl2] in 1969 has developed the new branch of bioionrganic chemistry: metal-based anticancer drugs. Metal complexes could inhibit the proliferation of cancer cell via the method binding with DNA and controlling the replication of DNA. Besides, Schiff base and acylhydrazone ligands are considered as the potential drugs to treat the desease about bacteria, tuberculosis and lepriasis. Hence, in this thesis, we synthesized some Schiff base and acylhydrazone ligands and twenty new complexses, which were structurally characterized by X-ray crystallographic methods. Several spectroscopic methods were used to investigate the interactions of complexes with DNA and BSA. In addition, some complexes with excellent biological activity were researched as potential anticancer drugs through some biological experiment, to study the DNA cleavage activity, anticancer ability and the mechanism of apoptosis.The main performance of this work are below:1. We synthesized two couple of chiral Schiff base ligands and twelve transition metal complexes. Considering the investigation of these complexes in DNA and BSA interaction, we selected the four copper complexes to research their ability in artificial nucleases and potential anticancer drugs. The four copper complexes exhibited excellent anticancer ability with IC50 values in micromole magnitude and similar with cisplatin. Based on some cell biological assays, we found that complexes 11-12 could arrest cancer cell cycle in G2/M phase, and induce the formation of ROS, which eventually up-regulate expressed the caspase 3 protein. Interestingly, though 11 and 12 could trigger cell apoptosis with the activation of caspases, the differential regulations of apoptotic related genes expression induced by complexes 11-12 revealed that the mechanisms of the enantiomers were distinct from each other. Complex 11 may induce apoptosis via extrinsic pathway with high expression of caspase-8, resulting in caspase-3 activation; however, complex 12 was able to induce cell apoptosis through intrinsic pathway of mitochondria with high expression of caspase-9, up-regulating Bax/Bcl-2 ratio and eventually activating caspase-3.2. We synthsized one trinuclear nickel complex and seven tetranuclear lanthanide complexes derived from the acylhydrazone ligand, which were structurally characterized by X-ray crystallographic methods. And the study of these complexes with DNA and BSA were measured via several spectroscopic methods. According to the MTT assay, we chose Ni, Gd and Dy complexes to study the mechanism of cell apoptosis induced by metal complexes. The experiments indicated that these complexes firstly induce the generation of ROS and then trigger apoptosis and death in cancer cells via the arrest of cell cycle. The assays indicated that complexes 13, 18 could arrest the G0/G1 phase of cell cycle, while complex 20 preferred to arrest the S phase to inhibit the proliferation...