'In vitro' antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters

Quercetin is well known to possess the strongest protective effect against UV light-induced lipoperoxidation. However, the absolute water insolubility of quercetin is a key step that may limit its bioavailability and, thus, its 'in vivo' employment as a photoprotective agent. The aim of the present paper was to evaluate 'in vitro' the antioxidant and photoprotective properties and the interaction with model membranes of three new semisynthetic quercetin derivatives, quercetin-3-O-acetate (Q-ac), quercetin-3-O-propionate (Q-pr) and quercetin-3-O-palmitate (Q-pal), obtained by esterification of the C-3 OH function with an aliphatic side-chain of different length. The antioxidant activity of quercetin and of its three esters was assessed in two 'in vitro' experimental models: (a) the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical: (b) UV radiation-induced peroxidation in multilamellar vesicles (MLVs). Differential scanning calorimetry on dimyristoylphosphatidylcholine MLVs and unilamellar vesicles was employed to investigate the interaction of the drugs tested with model membranes. Finally, the stability following UV light exposure and the lipophilicity and water solubility of quercetin and its three esters were examined. The findings obtained demonstrated that the esterification with an opportune aliphatic side chain of the OH function located at the C-3 position allows the production of new quercetin derivatives, which may be good candidates as photoprotective agents. In particular, one could speculate that the esterification with a short side-chain (such as in Q-ac and Q-prop) provides the suitable chemico-physical features not only to maintain the antioxidant and photoprotective effectiveness of the parent drug, but also to be able to migrate through the aqueous environment and to interact with and cross phospholipid membranes. (C) 2003 Elsevier B.V. All rights reserved.