Studies On Synthesis,Characterization And Antitumor Activity Of Cu(?),Pd(?),Pt(?)Complexs With 8-quinolinecarbaldehyde Thiosemicarbazide

Both quinoline alkaloids and thiourea derivatives are organic compounds containing nitrogen atom,which have good bioactivity,such as the obvious activity of antitumor,antibacterial and antiviral.Condensate compounds of quinoline and thiourea with rigid planar construction,have the characteristics of moderate molecular size,strong planarity and stability of binding with metal irons.Especially,it can produce strong biological synergistic effect after chelating with metal irons.Based on the above reasons,a series of complexes of 8-quinoline formaldehyde functioned with thiourea derivatives and their Cu(II),Pd(II),Pt(II)complexs were synthesized.We studied their inhibitory activity against tumor cell in vitro,and comparied to their toxicity of normal cells.The details are as follows :1.We outlined the research progress of the anti-tumor activity of platinum,palladium and copper metal complexes,and the biological activities of thiourea and its metal complexes.Based on these discussions,we illuminated the the basis of theme and the significance of this research.2.We synthesized seven 8-quinoline formaldehyde founctioned thiourea derivatives(L1~L7)and their twenty-one metal complexes coordinated with copper,palladium and platinum metal centre,which were got by the method of solution.All compounds were characterized by HRMS,NMR and IR.Four metal complexes of C1?C2?C8 and C9 were also analyzed by X-ray single crystal diffraction which are all mononuclear structures.The metal center of all compounds are coordinated with N atom of quinoline,thioureaimide,one S atom of thiocarbonyl,and one Cl ion,resulting in a planar quadrangula-rgeometry which are four-coordinate.In addition,the stabilities of some compounds under physiological conditions are tested by the HPLC method.The result show that the metal complexes can be stable in normal saline.3.We studied the inhibitory activity of growth and the toxicity of all the ligands and complexes against the tumor cells and normal cells by the MTT method.The results showed that copper complexes C1?C4?C7?C10?C13?C16?C19 have the best cytotoxic activity IC50 value of which are less than 3?M against tested several tumor cells.But it also is showed cell growth inhibition activity of broad-spectrum,namely,which have no selectivity of cell toxcity.Platinum complexes C3?C6?C12?C15?C18 and palladium complexes C2?C8?C14?C17?C20 also have some effect of inhibitiont against some tumor cells,but the overall effect of inhibition of tumor cell growth are less than all copper complexes.Palladium complex C14 containning two methyl group on N-4 site of the ligand showed a better inhibitory activity against the growth of MGC80-3 and Hep G2 cells,and their IC50 values were 16.63�1.2 ?M and 15.82�2.99 ?M,respectively.Palladium complex C20 which is benzyl on N-4 site of the ligand shows also better growth inhibition activity against A549 and SK-0V-3,and the IC50 values of which are 17.48�0.00 ?M,12.16�0.61 ?M,respectively.Platinum complexes C21 which is also benzyl on N-4 site of the ligand also shows better inhibition of the proliferation against MGC80-3,SK-OV-3 and Hep G2 cells.Their IC50 values are 15.63�1.28 ?M,14.69�1.44 ?M and 17.29�0.02 ?M respectively.