Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer ´s disease therapy.

Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer´s disease therapy. J Inorg Biochem. 2017 Nov 21;179:82-96 Authors: Hiremathad A, Chand K, Tolayan L, Rajeshwari, Keri RS, Esteves AR, Cardoso SM, Chaves S, Santos MA Abstract A series of (3-hydroxy-4-pyridinone)-benzofuran hybrids have been developed and studied as potential multitargeting drugs for Alzheimer's disease (AD). Their design envisaged mainly to mimic the donepezil drug, a marketed inhibitor of acetylcholinesterase (AChE), and to endow the conjugate molecules with extra-properties such as metal chelation, radical scavenging and inhibition of amyloid peptide (Aβ) aggregation. Thus, a set of eleven new hybrid compounds was developed and evaluated for chemical and biological properties, in solution and in neuronal cell environment. The results are discussed in terms of the type of substituents on both main moieties and the linker size. The closest similarity with donepezil, in terms of AChE inhibitory activity, was obtained for the O-benzyl-hydroxypyridinone hybrids containing a 2-methylene linker, although still less active than the drug. However, the free-hydroxypyridinone hybrids present higher activity for the Aβ aggregation inhibition, metal chelating capacity and radical scavenging activity. Overall, some compounds demonstrated capacity to exert a multiple action by hitting three- (7d) or four- (8d, 8f) pathophysiological targets of A...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research