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 alpha,alpha-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-G(2) 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. (C) 1999 Elsevier Science Ltd. All rights reserved.
Baldazzi, C., Calderoni, F., Marotta, E., Piani, S., Righi, P., Rosini, G., et al. (1999). Medium sized lactones with hypolipidaemic and antioxidant activity: synthesis and biological evaluation of promising dual-action anti-atherosclerosis drugs. BIOORGANIC & MEDICINAL CHEMISTRY, 7(2), 411-418 [10.1016/s0968-0896(98)00252-1].
Medium sized lactones with hypolipidaemic and antioxidant activity: synthesis and biological evaluation of promising dual-action anti-atherosclerosis drugs
Calderoni, Francesca;Marotta, Emanuela;Righi, Paolo;Rosini, Goffredo;Venturelli, Francesca
1999
Abstract
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 alpha,alpha-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-G(2) 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. (C) 1999 Elsevier Science Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
