Medium sized lactones with hypolipidaemic and antioxidant activity: synthesis and biological evaluation of promising dual-action anti-atherosclerosis drugs Original Research Article

Macrocyclic lactones 1a–b have been synthesized and their potential therapeutic value evaluated. The key structural feature of these active ‘chimera’ compounds is the 12-membered lactone ring that brings together the well-known polysubstituted hydroquinone moiety of antioxidants and the α,α-dimethyl substituted acyl residue of gemfibrozil. Lactones 1a–b showed better activity than probucol, a classical phenolic antioxidant, in preventing the Cu++-induced oxidative modification of human LDL. The hypolipidaemic activity of the new lactones, evaluated as the inhibition of lipids biosynthesis in Hep-G2 cells, was comparable to that of gemfibrozil. These features, added to the lack of cytotoxicity, make this new class of medium sized lactones promising dual-action drugs useful as anti-atherosclerosis agents. ©