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Flavonol-Based Carbon Monoxide Delivery Molecule with Endoplasmic Reticulum, Mitochondria, And Lysosome Localization.

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Light-triggered carbon monoxide (CO) delivery molecules are of significant current interest for evaluating the role of CO in biology and as potential therapeutics. Herein we report the first example of… Click to show full abstract

Light-triggered carbon monoxide (CO) delivery molecules are of significant current interest for evaluating the role of CO in biology and as potential therapeutics. Herein we report the first example of a metal free CO delivery molecule that can be tracked via confocal microscopy at low micromolar concentrations in cells prior to CO release. The NEt2-appended extended flavonol (4) localizes to the endoplasmic reticulum, mitochondria, and lysosomes. Subcellular localization of 4 results in CO-induced toxicity effects that are distinct as compared to a nonlocalized analog. Anti-inflammatory effects of 4, as measured by TNF-α suppression, occur at the nanomolar level in the absence of CO release, and are enhanced with visible-light-induced CO release. Overall, the highly trackable nature of 4 enables studies of the biological effects of both a localized flavonol and CO release at low micromolar to nanomolar concentrations.

Keywords: endoplasmic reticulum; delivery molecule; monoxide delivery; reticulum mitochondria; delivery; carbon monoxide

Journal Title: ACS medicinal chemistry letters
Year Published: 2022

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