Synthesis And Targeted Antitumor Effect Of Biotin-labeled Ruthenium(?)complexes

Purpaose:To synthesize a series of phenanthroline derivatives with different substituted alkyl group,optimize structure and study structure-activity relationship.To screen for a highly active and low toxic candidate compound and study the mechanism of its anti-tumor action.To synthesize the biotin-labeled ruthenium???complex.Methods:39ruthenium???compounds were synthesized and characterized by ESI-MS,NMR and X-ray crystal diffraction.And their antitumor activities and mechanism were preliminarily studied.Results:?1?Twenty-three arene ruthenium???compounds were synthesized in a yields above 90.0%under conditions of microwave irradiation heating for 30 min.The structure of all the compounds were characterized by ESI-MS,NMR and single-crystal X-ray diffraction.?2?The anticancer activities of arene ruthenium???compounds towards different tumor cells have been screened by MTT assay,with Fotemustine as positive comparison.The results showed that the antiproliferative effects of these complexes are cell-line specific.They exhibited a promising growth inhibition of C6 cells.We have found a compound as the most promising growth inhibitor against C6 glioma cells with an anti-tumor activity(IC₅₀)of 5.49?M,nearly 40-fold improvement over Fotemustine.In addition,the structure-activity relationship for the anticancer activity of these arene ruthenium???compounds was studied,and the results indicated that the electron donating group substituted derivatives exhibit better anticancer activity than the electron attracting group substituted derivatives,meanwhile,the group in ortho and para position made more contribution than meta position for anticancer activity.?3?Title compound 1 blocked the growth of glioma C6 cells through induction of S-phase arrest.?4?The synthetic method of biotin-labelled Ru???complex was determined.Then 16 complexes were characterized by ESI-MS,NMR and elemental analysis.?5?The spectroscopic properties of 4 biotin-labeled Ru??? complexes were further studied by spectroscopy assays.We found that all of them possess good photophysical properties,strong fluorescence intensity and large fluorescence quantum yield.