Neutral rhenium(i ) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization
DALTON TRANSACTIONS(2024)
摘要
Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six fac-[Re(NN)(CO)(3)(SR)] complexes, where (NN) is 2,2 '-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described fac-[Re(NN)(CO)(3)(OH2)](+) complexes; however, one of the complexes, fac-[Re(CO)(3)(phen)(SC(Ph)CH2C(O)OMe)] (3b), was active (IC50 similar to 10 mu M at 72 h treatment) in thiol-depleted MDA-MB-231 cells. Moreover, unlike fac-[Re(CO)(3)(phen)(OH2)](+), this complex did not lose activity in the presence of extracellular glutathione. Taken together these properties show promise for further development of 3b and its analogues as potential anti-cancer drugs for co-treatment with thiol-depleting agents. Conversely, the stable and non-toxic complex, fac-[Re(bipy)(CO)(3)(SC(Me)C(O)OMe)] (1a), predominantly localized in the lysosomes of MDA-MB-231 cells, as shown by live cell confocal microscopy (lambda(ex) = 405 nm, lambda(em) = 470-570 nm). It is strongly localized in a subset of lysosomes (25 mu M Re, 4 h treatment), as shown by co-localization with a Lysotracker dye. Longer treatment times with 1a (25 mu M Re for 48 h) resulted in partial migration of the probe into the mitochondria, as shown by co-localization with a Mitotracker dye. These properties make complex 1a an attractive target for further development as an organelle probe for multimodal imaging, including phosphorescence, carbonyl tag for vibrational spectroscopy, and Re tag for X-ray fluorescence microscopy.
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