Synthesis And Biological Activity Of Cu(?)complex Based On Water-soluble Cationic Porphyrin Acylhydrazone Ligands

In this thesis,we excogitated and synthesised eleven Cu?II?complexes based on various water-soluble cationic porphyrin acylhydrazone ligands by modifying peripheral substituents and metal ions on the core,have been well characterized via¹H NMR,ESI-MS and Elemental Anal.Multiple physicochemical approaches employed to measure the interaction of complexes with ct-DNA,in order to better understand carcinogenic activity at the cell level through the structure-function relationship,which will provide basis for further study of water-soluble copper porphyrin compunds in the aspects of medical research.1.We introduced the significance of research and the present synthesis condition of water soluble porphyrin compounds,the progress of interaction of them with DNA and anti-neoplasm in vitro.2.Three Cu-complexes containing multifarious 4-pyridyl-cationic porphyrin acylhydrazone ligands have been isolated and characterized?denoted as Cu-Por1^Cu-Por3?,and inspected the binding mode of them with ct-DNA carried out absorption titrations,ethidium bromide?EtBr?displacement assay,CD and induced circular dichroism?ICD?and viscosity measurement,indicating Cu-Por3 with higher binding constants compared to its analogues due to the steric hindrance at the acylhydrazone section;The capacity of inhibiting A549 and HepG2 carcinoma cells or Hs 578Bst normal cells growth in vitro of derivatives was adopted the colorimetric MTT assay,demonstrated that all tested complexes essentially have favorable inhibit activity in both cancer cells but interestingly show weak cytotoxicity on Hs 578Bst normal cells,which could be putted down to the tumor selectivity of porphyrin ring.In particular,the complex Cu-Por3 with a promising inhibit potency maybe be ascribe to the more easier displacement of Cl at the position of acylhydrazone might be easier replaced by other possible intracellular groups in acidic cancer cell environments which give rise to the mass of cellular internal medium.In order to better make clear the cytotoxicity,an extraction method was employed to quantified identify cellular absorb behavior of all complexes screened against two tumor cell lines.Additional,flow cytometric analysis depicted that the possible mechanism of the Cu-Por3induced A549 cells death mainly through later apoptotic and arrested G1 phase cells.3.Four Cu-complexes based on variety of 2-pyridyl-cationic porphyrin acylhydrazone ligands have been designed and synthesised?labeled as Cu-P1^Cu-P4?,and measured the binding mode of them with ct-DNA used absorption titrations,EtBr quenching assay,CD and ICD,viscosity measurement,indicating Cu-P4 with higher binding extent than the others boiled down to its smaller molecular size.Cytotoxicity studies indicated that Cu-P1^Cu-P4 could enrichment around the A549 and HepG2carcinoma cells compared with Hs 578Bst normal cells,therefore with good cytotoxic for two cancer cell lines.Particularly,the complex Cu-P4 with a promising inhibit potency to A549 maybe be ascribed to the more easier displacement ligands and molecular size.In addition,the possible mechanism of the Cu-P4 induced A549 cells death mainly through later apoptotic and arrested S phase through flow cytometric analysis.4.Four Cu-complexes based on cationic metalloporphyrin salicyloylhydrazone ligands have been designed and synthesised?marked as 1⁴?,and tested the binding mode of them with ct-DNA through absorption titrations,EtBr quenching assay,CD and ICD,viscosity measurement manifested that complex 2 interacts with ct-DNA stronger than the others,suggesting that Co?II?has no axial ligands of porphyrin plane plays a crucial role.MTT assay indicated that complex 1⁴ with good cytotoxic for the A549 and HepG2 cancer cell lines but weak for Hs 578Bst normal cells due to the selectivity of porphyrin ring.Especially,the IC₅₀ value of 1 is lower than its analogues against HepG2 cells when cultivated 72h,except the peripheral substituents electronic effect,the main reason is the Zn?II?has axial ligands of porphyrin core could be displaced by other possible intracellular groups and the mass cellular internal condition.The feasible mechanism of the conjugate 1 induced HepG2 cells death mainly accumulated S phase cells.