Unsymmetrical Vanadium Complexes With Multid Entate Ligand: Synthesis And Activity Study In Vitro

Recent decades, metal complexes have received much attention due to their hugepotentially as antitumor agents. Vanadium, as a trace bioelement, exhibit a variety of biologicalactivities such as antitumor, antimicrobial and insulin-enhancing effect and their complexesmay promote their pharmacological effect and reduce toxicity. Among the vanadiumcomplexes we synthesized before, complexes with Schiff base exhibit potential antitumoractivities, and found to be a promising compound with a potential in treatment of cancer.According to the previous research, it has been found that the activities of vanadium complexeswould much better with increasing the appending aromatic moiety. To find new complexeswith better bioactivities，we designed and synthesized some new oxovanadium complexesanalogues. The main contribution of the thesis includes following parts:1、In oder to examine the effects of aromatic moiety on the biological activities ofoxovanadium complexes, four novelty oxovanadium complexes,[VO(PAHN)(phen)](1),[VO(PAHN)(bpy)](2),[VO(PAH)(phen)](3) and [VO(PAH)(bpy)](4) were synthesised andcharacterized by elemental analysis, UV–vis spectroscopy, electrospray ionization massspectrometry (ESI-MS),IR spectroscopy,1H-NMR spectroscopy and13C-NMR spectroscopy. These complexes with calf-thymus DNA (CT-DNA) were investigated using UV-vis absorption,fluorescence spectra, viscosity measurements and thermal denaturation. Their cleavagereactions with pBR322supercoiled plasmid DNA were studied by gel electrophoresis. Inaddition, their cytotoxicity against MCF-7, SH-SY5Y and SK-N-SH tumor cells was assessedby MTT assay. The results show that the oxovanadium complex with larger aromatic planepossess stronger DNA-binding affinities with CT-DNA thus show higher cytotoxicities againsttumor cells..2、To investigate the influence of the introduction of larger aromatic ring and the existenceof electro withdrawing group in Schiff base ligands or auxiliary ligands substituted with1,10-phenanthroline on vanadium complexes biological activities, four oxovanadium complexeswith1,10-phenanthroline derivatives, VO(hntdtsc)(PHIP)(1),VO(hntdtsc)(DPPZ)(2),VO(satsc)(PHIP)(3), VO(satsc)(DPPZ)(4) were synthesized and characterized. Thecytotoxicity against MCF-7, SH-SY5Y and SK-N-SH tumor cells of these complexes wasassessed by MTT assay. The results showed that lager appending aromatic moiety possesshuger cytotoxic activities.3、We have also synthesized four oxovanadium complexes with different electricalsubstituent aimed to examine the effect on biological activities of them. The results indicatedthat complexes with electron-withdrawing group showed better antitumor activities. To fullyunderstand the mechanism involved in the biological activities of oxovanadium complexes bythe electronic-effects, further investigations will be needed to be conducted.