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
Binoy Kar, Shanooja Shanavas, Arun Karmakar, Apoorva H. Nagendra, Seshu Vardhan, Suban K. Sahoo, Bipasha Bose, Subrata Kundu, Priyankar Paira
Abstract
A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [ Ru 2 L1, Ru 2 L2, Ir 2 L1, Ir 2 L2, Re 2 L1, and Re 2 L2 ] 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 Ru 2 L1 and Ir 2 L2 are two proficient complexes among all, but Ru 2 L1 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 Ru 2 L1 -treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir 2 L2 -treated cells, which correlated with autophagy reticence.