NOVEL CURCUMIN DERIVATIVES WITH IMPROVED PHYSICOCHEMICAL PROPERTIES AND SURFACE-DECORATED NANOLIPOSOMES (WITH THE DERIVATIVES) WITH VERY HIGH AFFINITY FOR AMYLOID-B1-42-PEPTIDE.

摘要

Amyloid &bgr; (&Agr;&bgr;) aggregates are considered as possible targets for therapy and or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets &Agr;&bgr; plaques and interferes with their formation, suggesting a potential role for prevention or treatment of AD. In the present invention, curcumin-derivatives with improved physicochemical properties were synthesized and a "click chemistry" as well as a conventional liposome preparation method, were used to generate nanoliposomes decorated with the curcumin derivatives. These derivatives were designed to maintain the planar structure required for interaction with &Agr;&bgr;, as directly confirmed by Surface Plasmon Resonance experiments. Surface Plasmon Resonance experiments, measuring the binding of flowing liposomes to immobilized &Agr;&bgr;1-42, indicated that the liposomes exposing curcumin derivatives have extremely high affinity for &Agr;&bgr;1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions. The present invention describes the synthesis of the curcumin derivatives and the preparation and characterization of new nanoliposomes with a very high affinity for &Agr;&bgr;1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.