Can Polyamines be used to deliver chemotherapeutic drugs?

2019-08-01T12:20:52Z (GMT) by Vicki Emms
The naturally occurring polyamines putrescine, spermidine and spermine are found in almost all living cells. They are crucial to cell viability and play a key role in proliferation. As cancer cells exhibit an upregulated polyamine transport system (PTS) polyamine-drug conjugates are potential cancer-selective chemotherapeutics. This thesis describes the synthesis and biological evaluation of a series of polyamine conjugated 1,2,3-pyridyl triazole transition metal complexes, and efforts to tune the photophysical properties of these complexes for use in confocal microscopy. Cationic rhenium(I) tricarbonyl complexes with substituted pyridyl triazole ligands were synthesised to improve the performance of these probes for use in confocal microscopy. An electron withdrawing trifluoromethyl group significantly red-shifted the emission and increased the emission lifetime of the complexes with respect to the parent compound. A cationic rhenium spermine conjugate was found to have an IC50 of 7 μM cisplatin resistant A2780R ovarian cancer cells. Cyclometallated iridium polyamine conjugates were readily taken up by A549 lung adenocarcinoma cells and accumulated in the mitochondria, but not by polyamine transport deficient A549R cells. Similar results were seen with H157 cells and the PTS deficient cell line H157R. A triethylene glycol iridium conjugate was taken up similarly in both cell lines lending further support to the notion that uptake of the polyamine conjugates occurs via the PTS. Although iridium complexes were well tolerated in the dark, illumination led to rapid cell death by apoptosis, and may have potential for photodynamic therapy




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