Physical Sciences and Mathematics Commons^™

Cu(Ii) Phenanthroline-Phenazine Complexes Dysregulate Mitochondrial Function And Stimulate Apoptosis, Garret Rochford, Zara Molphy, Kevin Kavanagh, Malachy Mccann, Michael Devereux, Andrew Kellett, Orla L. Howe

Articles

Herein we report an in-depth study on the cytotoxic mechanism of action of four developmental cytotoxic copper(II) complexes: [Cu(phen)2]2+ (Cu-Phen); [Cu(DPQ)(Phen)]2+ (Cu-DPQ-Phen); [Cu(DPPZ)(Phen)]2+; and [Cu(DPPN)(Phen)]2+ (where Phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-f:20,30-h]quinoxaline, DPPZ = dipyrido[3,2-a:20,30-c]phenazine, and DPPN = benzo[i]dipyrido[3,2-a:20,30-c]phenazine). This complex class is known for its DNA intercalative properties and recent evidence—derived from an in vivo proteomic study—supports the potential targeting of mitochondrial function. Therefore, we focused on mitochondrial-mediated apoptosis related to cytotoxic activity and the potential impact these agents have on mitochondrial function. The Cu(II) complexes demonstrated superior activity regardless of aromatic extension within the phenazine ligand to the …