Affiliation:
1. Department of Chemistry & Biochemistry Utah State University 0300 Old Main Hill Logan UT 84322-0300 United States
2. Department of Animal, Dairy and Veterinary Sciences Utah State University 4815 Old Main Hill Logan UT 84322-4815 United States
Abstract
AbstractCarbon monoxide (CO) delivery molecules are of significant current interest as potential therapeutics, including for anticancer applications. A recent approach toward generating new types of materials‐based anticancer agents involves combining the Fenton reactivity of a redox active metal ion with CO delivery. However, small molecule examples of these types of entities have not been systematically studied to evaluate the combined effect on cellular toxicity. Herein we describe a Cu(II) flavonolato complex which produces anticancer effects through a combination of copper‐mediated reactive oxygen species (ROS) generation and light‐induced flavonol CO release. Confocal microscopy studies provide evidence of enhanced flavonol uptake in the copper flavonolato system relative to the free flavonol, which leads to an increased amount of CO delivery within cells. Importantly, this work demonstrates that a metal flavonolato species can be used to produce enhanced toxicity effects resulting from both metal ion‐induced Fenton reactivity and increased cellular uptake of a flavonol CO donor.
Funder
National Institutes of Health
National Science Foundation
Utah State University