AbdulSalam Safnas F, Gurjar Purujit N, Zhu Haizhou, Liu Jing, Johnson Emma S, Kadekaro Ana Luisa, Landero-Figueroa Julio, Merino Edward J
Department of Chemistry, University of Cincinnati, 404 Crosley Tower, Cincinnati, OH, 45221, USA.
Department of Dermatology, University of Cincinnati, Medical Sciences Building Room 1207A, 231 Albert Sabin Way, Cincinnati, OH, 45267-0592, USA.
Chembiochem. 2017 Oct 18;18(20):2007-2011. doi: 10.1002/cbic.201700341. Epub 2017 Aug 30.
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.
抗氧化疗法是一种很有前景的治疗策略，可保护DNA免受活性氧（ROS）造成的损伤。在此，我们报告了对羟基自由基具有选择性的新型自环化抗氧化剂。我们的机理研究表明，这些试剂在级联反应中与三当量的氧化剂反应，形成双环最终产物。在合成的试剂中，1 c在体外和细胞研究中表现出良好的性能。使用引发ROS产生的As O ，我们发现1 c可防止鸟嘌呤氧化产物2,2,4-三氨基-2H-恶唑-5-酮-2'-脱氧核糖核苷的形成，并降低细胞内活性氧水平。所述的自环化抗氧化剂是高效、灵活且可调的试剂，具有限制毒性氧化应激的潜力。
