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 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.

b Faculty of Science Department of Chemistry University of Hradec Kralove Hradec Kralove Czech Republic

c PEPITE EA4267 Laboratoire de Toxicologie Cellulaire University Bourgogne Franche Comté Besançon France

Department of Organic Chemistry and Inorganic Chemistry Alcalà University Madrid Spain

e Institute of Chemical Research Andrés M del Río Alcalà University Madrid Spain

f Instituto de Investigación en Neuroquímica Universidad Complutense de Madrid Madrid Spain

g Department of Biochemistry and Molecular Biology School of Pharmacy Plaza de Ramòn y Cajal Madrid Spain

h Laboratory of Medicinal Chemistry Madrid Spain

Neurosciences intégratives et cliniques Pôle Chimie Organique et Thérapeutique University Bourgogne Franche Comté Besançon France

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