Self‐Cyclizing Antioxidants to Prevent DNA Damage Caused by Hydroxyl Radical

Abstract

Antioxidant therapy is a promising treatment strategy for protecting DNA from the damage caused by reactive oxygen species (ROS). Here, we report new self-cyclizing antioxidant reagents that are selective for the hydroxyl radical. Our mechanistic investigation revealed that the reagents react with three equivalents of oxidant in a cascade reaction to form a bicyclic final product. Among the reagents synthesized, 1 c showed favorable properties in vitro and in cellular studies. Using As O , which triggers ROS production, we showed that 1 c prevents formation of the guanine oxidation product 2,2,4-triamino-2H-oxazol-5-one-2'-deoxyribonucleoside and lowers cellular levels of reactive oxygen. The described self-cyclizing antioxidants are efficient, flexible, and tunable reagents with the potential to limit toxic oxidative stress.

Apigenin Ameliorates Oxidative Stress-induced Neuronal Apoptosis in SH-SY5Y Cells

“…The •OH radical, which is the most reactive ROS, can be formed by a Fenton-type reaction, leading to severe damage in adjacent biomolecules [40]. The O 2 − radical is a precursor of other major ROS such as •OH radical and H 2 O 2 , which can damage biomolecules and alter physiological functions [41,42].…”