Synthesis Of Metal Complexes With Piperazine Derivatives And The Research Of Their Biological Activities

Telomerase was discovered by Carol Greider and Elizabeth Blackburn in 1984 from ciliate Tetrahaymana.telomerase inactive in normal cells or its active cannot be detected,but in most of the tumor cells have the telomerase activity,telomerase play a key role in cancer cells,therefore,growing number of scholars speculate that telomerase may be one of the best targets for cancer treatment,telomerase inhibitors are considered to be a kind of potential selective anticancer drugsIn this study,three lingads based on 4-（3,4-dichlorophenyl）piperazin4-（3,4-dichlorophenyl）piperazin 4-（3,4-dichlorophenyl）piperazin were synthesized respectively,then a serise of novel mononuclear complexes were synthesized,and have been characterized by IR spectroscopy,elemental analysis,and X-ray crystallography.These complexes are single-core structure,which belong to orthogonal crystal system and monoclinic system respectively.In order to reduce the workload of drug screening and to d explor the combining mode of complexes with telomerase molecules（3 du6）,AUTODOCK vina simulation program was used.The results showed that complexes 1,4,7 can combine with some amino acids of 3DU6.We also tested the in vitro biological activities of human telomerase enzyme inhibition,it show that complexes 1,4,7 all showed good inhibitory activity（IC50,23.21±0.78,10.12±1.13,31.34±1.06）,but lower than the positive control ethidium bromide（2.5±0.8）.and other complexes didn’t have telomerase enzyme inhibition.Cancer cell proliferation inhibition shows complexes IC₅₀of 1,4and 7 were 9.21±-0.7,8.13±0.61,16.5±0.23 respectively,and at the same level with the positive control cisplatin 2.2±-1.2.In normal cell toxicity test,the toxicity of 1 and 4 were all at the same level with.These results further reasonable optimization design is more effective for us pointed out the direction of the telomerase inhibitors.