Studies On Hexavanadate Hybrids Containing Amino Acid Esters-synthesis,Structure And Inhibitory Activity Of Common Tumor Cells

Polyoxometalates?POMs?,a kind of clusters formed by oxygen anions and former transition metal cations,have unique structures and versatile physical and chemical properties.POMs have shown excellent bioactivities and have potential applications in the fields such as antitumor and antivirus.However,the application of POMs in Pharmaceutical fields are set back by the low biocompatibility and strong toxicity of POMs.Incorporating POM clusters with bioactive molecules such as amino acids and peptides could improve the biocompatibility as well as enhance the drug activities of POMs,and thus it has great significance in the development of POM-based drugs.In this thesis,a series of hexavanadate hybrids containing amino acid esters have been synthesized by simple inorganic and organic reactions.The antitumor and antiviral activity of these derivatives are also studied.This paper mainly contains the following two parts:1.Fifteen POM hybrids incorporating different amino acid esters which based on pentaerythritol-derived hexavanadates[Bu₄N]₂[V₆O₁₃{?OCH₂?₃CCH₂OH}₂]were synthesized by a two-step approach.The structures of the products were fully characterized by single crystal X-ray diffraction,¹H-NMR spectra,ESI-MS and FT-IR.The eight compounds have got the single crystal structure.Two chiral structures of hybrids with chiral amino acid esters were acquired.2.The products were subjected to in vitro cytotoxic effects evaluation against Hela?cervical carcinoma?,Hep-2?laryngeal carcinoma?,RD?rhabdomyoma?,HepG2?hepatocellular liver carcinoma?and MCF-7?breast adenocarcinoma?cell lines by the standard MTT?3-?4,5-dimethylthiazol-2-yl?-2,5-diphenyl tetrazolium bromide?assay using 5-Fluorouracil as a positive control.The results of antitumor activity showed that grafting some amino acid esters onto the cluster can enhance the antitumor activity of hexavanadate.The inhibitory effects of hybrids incorporating?-ala tert-butyl ester and and L-ala methyl ester on tumor cells were significantly better than 5-fluorouracil.The IC₅₀ values of these two compounds were less than 30?mol/L in HeLa,Hep-2 and RD cells.These results provide a new thought in the design and synthesis of POM-based drugs.