P4-280: Marine polyunsaturated fatty acids as BACE inhibitors

Abstract

The marine environment represents an enormous resource for the discovery of potential chemotherapeutic agents. It is the source of a large group of structurally unique natural products that are mainly accumulated in invertebrates such as sponges, tunicates, bryozoans, and molluscs. Several of these compounds show pronounced pharmacological activities and are interesting candidates for new drugs in several areas of treatment. Within a systematic screening program aimed at isolating compounds from marine organisms showing biological activities relevant for preventing and/or treating neurodegenerative diseases, such as Alzheimer's disease (AD), we have found that isopropanolic extracts from a number of marine organisms, including sea stars and blue crabs, presented interesting biological activities, particularly BACE (β site AβPP cleaving enzyme) inhibition. This enzyme is involved in formation of amyloid β peptide and has become an important target for the development of therapeutic compounds against AD. Isolation and structure elucidation led to find out that some of the compounds which were responsible for the inhibitory activity in the initial isopropanolic extracts were polyunsaturated fatty acids (PUFAs). Particularly, the monodimensional and bidimensional proton and carbon nuclear magnetic resonance studies and mass spectra performed to elucidate the structure of the more frequently isolated compounds correspond to those of known PUFAs, namely linolenic acid, linoleic acid, eicosapentaenoic acid and arachidonic acid. The positive results of the biological activity obtained from the natural extracts were confirmed by the additional testing of some commercially available PUFAs.