Design and synthesis of coumarin-3-acylamino derivatives to scavenge radicals and to protect DNA

• Several coumarin-3-acylamino derivatives were synthesized for the first time.
• Antioxidant abilities of coumarin-3-acylamino derivatives were evaluated.
• Hydroxyl and ortho-methoxy group can enhance the antioxidant abilities remarkably.
• Structure–activity relationships give interesting results.

In this study, a series of coumarin-3-acylamino derivatives containing phenethylamine moiety or tyramine moiety were synthesized and their antioxidant activities were evaluated by Cu2+/glutathione(GSH)-, OH- and 2,2′-azobis(2-amidinopropane hydrochloride)(AAPH)-induced oxidation of DNA. It was found that both hydroxyl and ortho-methoxy groups at A ring, hydroxyl group at B ring and peptide bond can enhance the abilities of coumarin-3-acylamino derivatives to protect DNA against OH- and AAPH-induced oxidation. Moreover, these coumarin-3-acylamino derivatives were employed to scavenge 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+). We found that tyramine moiety, hydroxyl and ortho-methoxy are the key groups to enhance the activities of antioxidants to quench ABTS+. Therefore, tyramine linked with coumarin-3-carboxyl acid which containing hydroxyl and ortho-methoxy exhibited powerful antioxidant abilities.

Capacities of coumarin-3-acylamino derivatives to scavenge ABTS+· radical and to protect DNA against AAPH-induced oxidation.Figure optionsDownload as PowerPoint slide