Introducing ferrocene into imidazo[1,2-a]pyridine by Groebke three-component-reaction for scavenging radicals and inhibiting DNA oxidation

Abstract

With 2-aminopyridine or quinoline, seven aldehydes, and five isocyanides as reactants, sixteen imidazo[1,2-a]pyridines or quinolines were synthesized by using Groebke three-component-reaction (3CR). The radical-scavenging ability was evaluated by quenching 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+·), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radicals, respectively. Compounds consisting of double ferrocenyl groups coupled with quinoline and ester moieties showed good potencies for scavenging ABTS+· and DPPH, while phenolic hydroxyl groups activated the corresponding imidazo[1,2-a]pyridines to react with galvinoxyl radical. Moreover, the oxidation of DNA was caused by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), and all of the synthetic compounds were found to inhibit the DNA oxidation. Especially, the scaffold of imidazo[1,2-a]pyridine exhibited antioxidative effect on the DNA oxidation, while the most active compound was ascribed to double ferrocenyl groups incorporating with imidazo[1,2-a]quinoline. The present results showcased that the ferrocenyl group attaching to the scaffold of imidazo[1,2-a]pyridine or quinoline was beneficial for the antioxidative effect.