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Self‐Cyclizing Antioxidants to Prevent DNA Damage Caused by Hydroxyl Radical
Author(s) -
AbdulSalam Safnas F.,
Gurjar Purujit N.,
Zhu Haizhou,
Liu Jing,
Johnson Emma S.,
Kadekaro Ana Luisa,
LanderoFigueroa Julio,
Merino Edward J.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700341
Subject(s) - reagent , reactive oxygen species , chemistry , antioxidant , dna damage , oxidative stress , radical , guanine , hydroxyl radical , dna oxidation , combinatorial chemistry , dna , biochemistry , organic chemistry , nucleotide , gene
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 2 O 3 , which triggers ROS production, we showed that 1 c prevents formation of the guanine oxidation product 2,2,4‐triamino‐2 H ‐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.