Synthesis, DNA-binding, Cleavage And Anticancer Activity Studies Of Some Vanadium Complexes

For years, many transition-metal complexes have been exploited for the design of newdrugs due to their diverse biological activities. Vanadium complexes have been found topresent antibacterial, insulin-enhancing and antiparasitic effects. Especially, vanadiumcomplexes have also been found to present prominent anticancer activities in recent years,therefore, it is highly necessary to investigate DNA-binding interaction for further study ofanticancer activities of vanadium complexes. In addition, Schiff bases have been extensivelystudied because of their potential antibacterial, antifungal, antimalarial and anticancer activities.Reports shown that the presence of a rigid aromatic system in the schiff base structure givesrise to particular spectroscopic properties, which make it a potential probe for nucleic acids. Inthis context, a series of oxovanadium complexes have been designed and synthesized.DNA-binding properties, chemical nuclease activity and anticancer activity have also beenstudied systematically. The main contents of the thesis are as follow:1. In the present work, eight vanadium complexes, VO(hntdtsc)(p), VO(hntdtsc)(b),VO(satsc)(p), VO(satsc)(b), VO(deasaa)(p), VO(mosaa)(p), VO(saa)(p) and VO(clsaa)(p)which use2-hydroxy-1-naphthaldehyde thiosemicarbazone, salicylaldehyde thiosemicarbazon-es and salicylidene anthranilic acid incorporating different groups as main ligands and the1,10-phenanthroline or2,2’-dipyridyl as second ligands were synthesized and characterized byelemental analysis, IR, UV-Vis, ESI-MS and1H NMR.2. The interaction style and binding intensity of all synthesized complexes with CT-DNA were investigated using spectroscopy and fluid mechanics. The binding strength with CT-DNAwas also analyzed through the size of aromatic conjugated system as well as spatial sterichindrance. The results indicate that all these eight complexes interact with CT-DNA throughintercalative mode. The binding affinity of the vanadium complexes (Kb) decreases in theorder:(1) VO(hntdtsc)(p)> VO(hntdtsc)(b)> VO(satsc)(p)> VO(satsc)(b);(2) VO(saa)(p)>VO(mosaa)(p)> VO(clsaa)(p)> VO(deasaa)(p). The results also show that the binding affinityof these complexes bearing2-hydroxy-1-naphthaldehyde thiosemicarbazone was larger thanthat of those with corresponding salicylaldehyde thiosemicarbazones. The DNA-bindingaffinity of synthesized complexes based on1,10-phenanthroline chosen as the ministrantligand was larger than that of those based on bipyridine as the ministrant ligand. Besides, thebinding strength of these synthesized complexes bearing salicylidene anthranilic acid with nogroups was larger than that of those with groups such as–N(C2H5)2,–OCH3and Cl.3. The chemical nuclease activities of these complexes were studied. The results implythat these complexes could prominently enhance the oxidative cleavage of supercoiled pBR322DNA under physiological conditions in the presence of H2O2.4. The cytotoxicity of all synthesized complexes and corresponding ligands was assessedby MTT assay. Comparing the anticancer activities of the ligands and the correspondingcomplexes, it can be concluded that the anticancer activities against selected two tumor celllines have been remarkably enhanced when ligands coordinated with the V metal center. It wasfound that the IC50values of VO(hntdtsc)(p) and VO(saa)(p) are bigger than that of othersynthesized compounds. It is notable that complex VO(hntdtsc)(p), as compared with othertested complexes, possessed the most potent inhibitory effect against the cell lines. And its IC50value which is very close to that of cisplatin indicated its high cytotoxic effects against humancancer cells.The above results may provide some new ideas and material bases for design andsynthesis of novel non-platinum metallic anticancer drugs targeting DNA molecule.