Luminescent 11-{Naphthalen-1-yl}dipyrido[3,2-a:2′,3′-c]phenazine-Based Ru(II)/Ir(III)/Re(I) Complexes for HCT-116 Colorectal Cancer Stem Cell Therapy

Abstract

Due to a number of unpleasant considerations, marketed drugs have steadily lost their importance in the treatment of cancer. In order to find a viable cancer cell diagnostic agent, we therefore focused on metal complexes that displayed target adequacy, permeability to cancer cells, high standard water solubility, cytoselectivity, and luminescent behavior. In this aspect, luminescent 11-{naphthalen-1-yl} dipyrido [3,2-a:2′,3′-c] phenazine based Ru(II)/Ir(III)/Re(I) complexes have been prepared for HCT-116 colorectal cancer stem cell therapy. Our study successfully established the possible cytotoxicity of IrL complex at different doses on HCT-116 colorectal cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis of the complex IrL showed that the molecule was subcellularly localized in the nucleus and other regions of the cytoplasm, where it caused nuclear DNA damage and mitochondrial dysfunction. The level of BAX and Bcl-2 was further quantified by qRT-PCR. The expression of proapoptotic BAX showed increased expression in the complex IrL-treated cell compared to the control, indicating the potential of complex IrL for apoptotic induction. Upon further validation, complex IrL was developed as an inhibitor of autophagy for the eradication of cancer stem cells.

Synthesis, characterization, photophysical and electrochemical properties, and biomolecular interaction of 2,2′-biquinoline based phototoxic Ru(ii)/Ir(ii) complexes

“…The K sv values were found to be 0.129 × 10 6 M −1 and 0.205 × 10 6 M −1 for complexes RuBQ and IrBQ , respectively (Table 2, eqn (iv), see the ESI† for details). 20,25…”

“…25 mg of ligand BQ (1 equiv) and 30 mg of [Ru II 2 (η 6 - p cym) 2 (Cl) 4 ] (0.5 equiv) were utilized to synthesize RuBQ , as described in earlier work. 25 A brown coloured complex was formed.…”

“…This suggested the possibility of major and minor groove binding. 25,26 Ethidium bromide displacement assay. The intercalation of the synthesized complexes to ct-DNA was further proved by an EtBr displacement assay recorded in a spectrofluorometer.…”

“…The K sv values were found to be 0.129 × 10 6 M −1 and 0.205 × 10 6 M −1 for complexes RuBQ and IrBQ, respectively (Table 2, eqn (iv), see the ESI † for details). 20,25 Viscosity measurement. The effects of the relative specific viscosity by addition of the complexes in ct-DNA solutions were investigated with the help of an Ostwald viscometer following a hydrodynamic method.…”

“…Using the Scatchard eqn (vi) (see the ESI † for details), we were able to determine the total number of binding sites for these complexes and their binding constants (Table 4). 5,20,25,27 Singlet oxygen generation ( 1 O 2 )…”