Interaction of Cyclometallated Ru(II) Drugs with Glutathione
Loading...
Date
2013-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
Photodynamic therapy (PDT) utilizing light to activate metal complexes has emerged as an alternative strategy of cancer treatment that imparts greater specificity of toxicity. In the realm of PDT, light-activated inorganic metal complexes that covalently bind DNA have come to the fore as potential anticancer therapies. The cyclometallated complex cis-[Ru(phpy)(phen)(CH3CN)2]+ (1: phpy– = deprotonated 2-phenylpyridine, phen = 1,10-phenanthroline) was recently found to inhibit tumor growth in mice with fewer major side effects. Treatment of the human ovarian cancer cell line OVCAR-5 with 1, resulted in a fourteen-fold increase in toxicity in irradiated conditions as compared to dark conditions. Despite this large photoinduced increase in toxicity of 1, the photophysical properties as well as the photoactivating mechanism are not fully understood; hence, both have been investigated for complex 1 and for the analog cis-[Ru(phpy)(bpy)(CH3CN)2]+ (2: bpy = 2,2´- bipyridine). Within the cell, there is the possibility of ligand exchange occurring in the presence of coordinating solvent and a large intracellular pool of reduced glutathione (GSH), therefore the possible role that GSH may play in facilitating the production of toxic species was explored for 1 and 2. Both complexes 1 and 2 undergo ligand exchange in the presence of GSH in the dark. The observed cytotoxicity of 1 may be explained by both GSH-facilitated ligand dissociation and photo-induced ligand exchange.
Description
Keywords
photochemistry, ruthenium, cancer, glutathione, light-activated, photodynamic therapy