2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents#

Abstract

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [Ru₂L1, Ru₂L2, Ir₂L1, Ir₂L2, Re₂L1, and Re₂L2] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru₂L1 and Ir₂L2 are two proficient complexes among all, but Ru₂L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕ_f) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru₂L1-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir₂L2-treated cells, which correlated with autophagy reticence.