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

  • ACS Med Chem Lett. 2022 Feb 1;13(2):236-242. doi: 10.1021/acsmedchemlett.1c00595.
Livia S Lazarus  1 ,  C Taylor Dederich  1 ,  Stephen N Anderson  1 ,  Abby D Benninghoff  2 ,  Lisa M Berreau  1
Affiliations
  • 1. Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322-0300, United States.
  • 2. Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah 84322-4815, United States.
PMID: 35178180 DOI: 10.1021/acsmedchemlett.1c00595
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.

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