Inhibition Of Telomerase Activity Studies Of Ruthenium (Ⅱ)-porphyrin Complexes And The Involvement Of Mitochondria To Ruthenium Complexes-induced Cancer Cell Apoptosis Studies.

A series of Ruthenium(â…¡) porphyrin complexes have been synthesized,characterized and studied for their biological activities,including G-quadruplex DNA binding properties and in vitro anticancer activities.The possible antitumor mechanisms have also been investigated in this dissertation.Many interesting results have been obtained,which included:1.Four types of ruthenium porphyrin complexes have been synthesized.All of the newly synthesized complexes have been characterized by elemental analysis,ESI-MS and NMR.2.The G-quadruplex DNA binding properties of these complexes have been investigated by UV-Vis,competitive binding with EB,CD spectra and thermal denaturalization.We also examined the telomerase activities of the synthetic complexes.The results show that the ruthenium porphyrin complexes can bind to and stabilize G-quadruplex DNA.3.The in vitro anticancer activities of the ruthenium porphyrin complexes were screened by MTT assay.The results show that ruthenium porphyrin complexes could inhibit the growth of cancer cells in a time- and dose-dependent manner.4.Loss of mitochondrial membrane potential in A375 cells after ruthenium porphyrin complexes treatment were detected by JC-1 staining assay.These results indicate that treatments of complex 1 and complex 3 induced a dose-dependent depletion of mitochondrial membrane potential in A375 cells,indicating the involvement and contribution of mitochondria to ruthenium complexes-induced cell apoptosis.5.The effects of ruthenium porphyrin complexes on intracellular ROS generation were evaluated by DCF fluorescence assay.The results indicate that ruthenium porphyrin complexes can inhibited the growth of ROS generation.The antioxidant activities of ruthenium porphyrin complexes were evaluated by using two different free radical scavenging assays,namely,the ABTS assay and DPPH assay.