Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cance Show more
Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports tumor cell survival, drug resistance, and metabolic reprogramming. Recent studies demonstrate that NRF2 enhances glutathione (GSH) synthesis, induces detoxifying enzymes, and upregulates drug efflux transporters, collectively contributing to resistance against chemotherapy and targeted therapies. The inhibition of NRF2 using small molecules or dietary phytochemicals has shown promise in restoring drug sensitivity in preclinical cancer models. This review highlights the dual role of NRF2 in redox regulation and cancer therapy, emphasizing its potential as a therapeutic target. While targeting NRF2 offers a novel approach to overcoming treatment resistance, further research is needed to enhance specificity and facilitate clinical translation. Show less
Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules wh Show more
Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including small Stokes shifts, short emission lifetimes, and susceptibility to photobleaching. To explore alternative lysosome targeting imaging agents we have used a rhenium based phosphorescent platform which has been previously demonstrated to have an improved Stokes shift, a long lifetime emission, and is highly photostable. Rhenium complexes containing morpholine substituted ligands were designed to accumulate in acidic compartments. Two of the three complexes prepared exhibited bright emission in cells, when incubated at low concentrations (20 μM) and were non-toxic at concentrations as high as 100 μM, making them suitable for live cell imaging. We show that the rhenium complexes are amenable to chemical modification and that the morpholine targeted derivatives can be used for live cell confocal fluorescence imaging of endosomes–lysosomes.
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Ten manganese(I) tricarbonyl diimine complexes bound to variably functionalised 5‐aryl‐tetrazolato ligands were prepared, and their photochemical properties were investigated. Upon exposure to light a Show more
Ten manganese(I) tricarbonyl diimine complexes bound to variably functionalised 5‐aryl‐tetrazolato ligands were prepared, and their photochemical properties were investigated. Upon exposure to light at 365 nm, each complex decomposed to its free diimine and tetrazolato ligands, simultaneously dissociating three CO ligands, as evidenced by changes in the IR spectra of the irradiated complexes over time. The anti‐bacterial properties of one of these complexes were tested against Escherichia coli. While the complex displayed no effect on the bacterial growth in the dark, pre‐irradiated solutions inhibited bacterial growth. Comparative studies revealed that the antibacterial properties originate from the presence of free 1,10‐phenanthroline. Show less