The Effect Of Metal Ions On The Stability Of G-quadruplex With Or Without A Small-molecule Ligand:6H-indole[2,3-b]quinoxaline Derivative

As one of the most difficult disease to treat, the cancer has a serious threat to human lifeand health, so how to prevent and treat cancer becomes a problem to be solved in the medicalcommunity. Rich guanine(G) at the end of telomere can form G-quadruplex, and theformation and stabilization can inhibit the activity of telomerase, then it can achieve the goalof treatment of tumor. So the research of ligands which can stabilize G-quadruplex has beenwidely concerned.In recent years, many ligands have been synthesized to stabilize G-quadruplex, but fewcan be validated as antitumor drugs. Therefore, the microenvironment of tumor cells and theconcentration of metal ions in the cell should be considered. For example, copper ionconcentration in the tumor cells is higher than normal cells, and20%of the copper ions existin the nucleus.In this thesis, the effects of metal ions on the stability of G-quadruplex with or without aligand：6H-indole[2,3-b]quinoxaline derivative were researched through CD spectroscopy.The results showed some metal ions Al3+、Cd2+、Co2+、Cu2+、Fe2+、Fe3+、Ni2+、Ag+、Hg2+can make G-quadruplex unstable with or without ligand, and Ba2+can reverse the unstableeffect. These results suggested that the development of G-quadruplex ligands as antitumordrugs must take the destabilizing effects of metal ions into account. In light of highconcentrations of Cu2+in tumor cells, we further developed a fluorogenic probe for Cu2+. Ithas been found that Cu2+has good selectivity for FITC probe. When the concentration of Cu2+was10nmol/L, FITC probe could distinguish Cu2+from other metal ions. FITC probe couldalso detect Cu2+inside cells. This study thus provides a versatile tool for exploring thebiology of metal ions inside cells.