New lipophenols prevent carbonyl and oxidative stresses involved in macular degeneration

Dry age-related macular degeneration and Stargardt disease undergo a known toxic mechanism caused by carbonyl oxidative stresses (COS). This is responsible for accumulation in the retinal pigment epithelium (RPE) of A2E, main pyridinium bis-retinoid lipofuscin component. Previous studies have shown that stress cells could be reduced an alkyl-phloroglucinol-DHA conjugate (lipophenol). Here, we performed rational design different families lipophenols to conserve anti-carbonyl activities improve antioxidant properties. Five synthetic pathways leading alkyl-(poly)phenol derivatives, with phloroglucinol, resveratrol, catechin quercetin as backbone, linked poly-unsaturated fatty acid, are presented. These were evaluated ARPE-19 cell line their anti-COS properties structure-activity relationship study proposed. Protection against A2E toxicity was assessed four best candidates. Finally, interesting most promising lipophenol confirmed primary RPE cells.