Microwave-assisted Sonogashira Reaction With The Preparation Of Ethynyl-containing Ruthenium(â…¡) Complexes And Their Antitumor Activity

The success of cisplatin as anticancer agents has stimulated a search for other active transition metal anticancer complexes, and ruthenium in particular has attracted recent attention. But the application limitations of cisplatin have prompted a search for more effective and less toxic alternative metal-based antitumor agents. As well as known, Ru(II) complexes have been considered as one of the most promising metallic antitumor drugs. Especially, ruthenium(II) polypyridyl complexes have been paid more and more attention for the diversity of structure and wide applications.The importance of this study is applying microwave-assisted heating method to introduce different modified ethynyl units for Ru(II) polypyridyl complexes. In addition, we make a preliminary research on the inhibitory action of this kind of complexes to MCF-7cells in vitro and the interaction between the complexes and G-quadruplex DNA.The contents of the thesis are carried out as following:1. Using [Ru(bpy)2(p-BrPIP)](C104)2and [Ru(phen)2(p-BrPIP)](ClO4)2as raw material, apply microwave-assisted heating method to prepare6Ru(II) polypyridyl complexes modified by different ethynyl units through Sonogashira reaction, the structures of these complexes were characterized by ESI-MS, XH NMR,13C NMR and1H-1H COSY, and the research results agree well with the theoretical values. All the compounds have not been reported in the literature. 2. The inhibitory action of these6Ru(Ⅱ) polypyridyl complexes to MCF-7cells was tested by MTT methods, the results revealed that the Ru(II) polypyridyl complexes may inhibit tumor cell growth in varying degrees, the value of IC50all less than50μM, especially, the IC50of complex Id is6.76μM, below about180times of positive control NAMI-A and similar to taxol.3. Utilize Electronic Absorption Spectrum, Electron Emission Spectrum, CD Spectrum and Thermotropy to respectively research the role of molecular recognition to G-quadruplex (c-myc) of Ru(Ⅱ) complexes2b,2c and2d. The results show that four Ru(Ⅱ) complexes can induce information and stable the structure of G-quadruplex (c-myc) observably. It seems quite possible to develop as a potential agent of telomerase inhibitors.These results demonstrated that application of microwave-assisted by Sonogashira reaction can prepare Ru(Ⅱ) polypyridyl complexes modified by different ethynyl units with high efficiency. All prepared Ru(Ⅱ) polypyridyl complexes modified by different ethynyl units were great candidate drugs, which have potential antitumor activity application prospect. For the mechanism of Ru(Ⅱ) polypyridyl complexes modified by different ethynyl units binding with DNA need further research.