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

Autor: Kar B; Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India., Shanavas S; Department Stem Cells and Regenerative Medicine Centre, Institution Yenepoya Research Centre, Yenepoya University, University Road, Derlakatte, Mangalore, 575018 Karnataka, India., Karmakar A; Materials Chemistry Laboratory for Energy, Environment and Catalysis, Electrochemical Process Engineering (EPE) Division, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi, Tamil Nadu 630003, India., Nagendra AH; Department Stem Cells and Regenerative Medicine Centre, Institution Yenepoya Research Centre, Yenepoya University, University Road, Derlakatte, Mangalore, 575018 Karnataka, India., Vardhan S; Department of Applied Chemistry, S. V. National Institute of Technology (SVNIT), Ichchanath Surat, Gujarat 395007, India., Sahoo SK; Department of Applied Chemistry, S. V. National Institute of Technology (SVNIT), Ichchanath Surat, Gujarat 395007, India., Bose B; Department Stem Cells and Regenerative Medicine Centre, Institution Yenepoya Research Centre, Yenepoya University, University Road, Derlakatte, Mangalore, 575018 Karnataka, India., Kundu S; Materials Chemistry Laboratory for Energy, Environment and Catalysis, Electrochemical Process Engineering (EPE) Division, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi, Tamil Nadu 630003, India., Paira P; Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2024 Jul 11; Vol. 67 (13), pp. 10928-10945. Date of Electronic Publication: 2024 May 29.
DOI: 10.1021/acs.jmedchem.4c00406
Abstrakt: 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.
Databáze: MEDLINE