Luminescent iridium(iii) complexes as COX-2-specific imaging agents in cancer cells

Abstract

Two luminescent iridium(iii) complexes, 1 and 2, were synthesized and evaluated for their ability to probe COX-2 in human cancer cells. This is the first application of iridium(iii) complexes as imaging agents for COX-2. We demonstrate that complex 1 differentiates cancer cells from normal cells with high stability and low cytotoxicity.

Metamizole (dipyrone) – cytotoxic and antiproliferative effects on HeLa, HT-29 and MCF-7 cancer cell lines

“…In the literature there are diverse data considering COX expression in different cell lines [66][67][68][69]. HeLa, HT-29 and MCF-7 cell lines have high expression of COX-1, but relatively low of COX-2 [70][71][72]. Metamizole and its metabolites have been shown to inhibit COX-1 and COX-2 activity by a different pathway than the classical aspirin-like NSAIDs mechanism [73].…”

Group 8–9 Metal-Based Luminescent Chemosensors for Protein Biomarker Detection

“…Instead, a non-covalent interaction between the probe and the analyte changes the local environment of the probe, triggering a luminescence response [41,42]. In contrast, in the covalent mechanism, a chemical reaction takes place between a functional group on the sensing probe and the target analyte [43,44], producing novel products with different optical properties, such as wavelength and emission intensity, compared to the starting materials [45].…”

“…Ma, Leung and co-workers have recently developed two luminescent iridium(III) complexes 5a and 5b (Fig. 5a) for the sensing of COX-2 in human cancer cells [44]. These complexes conjugate the well-known COX-2 inhibitor, indomethacin, on an iridium(III) scaffold.…”

“…In the presence of various nonprotein substances, including detergents (Triton X-100 and SDS), chelating agent ethylenediaminetetraacetic acid (EDTA) and inorganic salts (calcium chloride, sodium phosphate, zinc chloride, cobalt chloride, sodium acetate, sodium chloride), only a minor change in luminescence intensity is observed, further demonstrating the selectivity of complex 6 for BSA. Additionally, complex 6 could also be employed as a stain for proteins in an SDS-PAGE gel, enabling the detection of as little as 1.5 ng of protein [44]. Reprinted figure with permission from copyright (2017) Royal Society of Chemistry per band, making it a safer and less costly alternative to silver staining methods [69].…”

JAG1 loss‑of‑function mutations contributed to Alagille syndrome in two Chinese families

“…Boyer-Di Ponio et al (15), showed that the missense mutant protein C284F as well as truncated proteins E1003X and Δ4 impaired activation of Notch signaling, suggesting that a dominant-negative effect mechanism may also explain the impaired biological function of some ALGS mutations. Biomarker detection was widely used to monitor the development of certain diseases (17)(18)(19). The finding that the developing heart was more sensitive to a decreased dosage of JAG1 than the developing liver implicates JAG1 as a plausible candidate biomarker for cardiac severity in ALGS (20).…”