2-Aryl-1<i>H</i>-imidazo[4,5-<i>f</i>][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 [<b>Ru</b>_<b>2</b><b>L1</b>, <b>Ru</b>_<b>2</b><b>L2</b>, <b>Ir</b>_<b>2</b><b>L1</b>, <b>Ir</b>_<b>2</b><b>L2</b>, <b>Re</b>_<b>2</b><b>L1</b>, and <b>Re</b>_<b>2</b><b>L2</b>] 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 <b>Ru</b>_<b>2</b><b>L1</b> and <b>Ir</b>_<b>2</b><b>L2</b> are two proficient complexes among all, but <b>Ru</b>_<b>2</b><b>L1</b> 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 <b>Ru</b>_<b>2</b><b>L1</b>-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in <b>Ir</b>_<b>2</b><b>L2</b>-treated cells, which correlated with autophagy reticence.