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Donepezil?+?chromone?+?melatonin hybrids as promising agents for Alzheimer's disease therapy.

ABSTRACT: We describe herein the design, multicomponent synthesis and biological studies of new donepezil?+?chromone?+?melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50?=?11.90?±?0.05?nM), moderate hAChE (IC50?=?1.73?±?0.34??M), hMAO A (IC50?=?2.78?±?0.12??M), and MAO B (IC50?=?21.29?±?3.85??M) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil?+?Chromone?+?Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure.

SUBMITTER: Pachon-Angona I

PROVIDER: S-EPMC6366423 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Donepezil + chromone + melatonin hybrids as promising agents for Alzheimer's disease therapy.

Pachón-Angona Irene I Refouvelet Bernard B Andrýs Rudolf R Martin Helène H Luzet Vincent V Iriepa Isabel I Moraleda Ignacio I Diez-Iriepa Daniel D Oset-Gasque María-Jesús MJ Marco-Contelles José J Musilek Kamil K Ismaili Lhassane L

Journal of enzyme inhibition and medicinal chemistry 20191201 1

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE (IC50 = 1.73 ± 0.34 μM), hMAO A (IC50 = 2.78 ± 0.12 μM), and MAO B (IC50 = 21.29 ± 3.85 μM) inhibition, while keeping a strong ...[more]

PMID: 30712420

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