Hiremathad_2017_J.Inorg.Biochem_179_82

Reference

Title : Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer s disease therapy - Hiremathad_2017_J.Inorg.Biochem_179_82
Author(s) : Hiremathad A , Chand K , Tolayan L , Rajeshwari , Keri RS , Esteves AR , Cardoso SM , Chaves S , Santos MA
Ref : J Inorg Biochem , 179 :82 , 2017
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 (Abeta) 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 Abeta 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 AD. Furthermore, the compounds showed neuroprotective effects in neuronal cells subjected to model stressors of AD, but not significant dependence on the substituent groups. Importantly, the compounds evidenced drug-likeness properties, including good membrane permeability.

PubMedSearch : Hiremathad_2017_J.Inorg.Biochem_179_82
PubMedID: 29182921

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Citations formats

Hiremathad A, Chand K, Tolayan L, Rajeshwari, Keri RS, Esteves AR, Cardoso SM, Chaves S, Santos MA (2017)
Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer s disease therapy
J Inorg Biochem 179 :82

Hiremathad A, Chand K, Tolayan L, Rajeshwari, Keri RS, Esteves AR, Cardoso SM, Chaves S, Santos MA (2017)
J Inorg Biochem 179 :82