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

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 34; no. 1; pp. 479 - 489
• Main Authors: Pachon-Angona, Irene, Refouvelet, Bernard, Andrys, Rudolf, Martin, Helene, Luzet, Vincent, Iriepa, Isabel, Moraleda, Ignacio, Diez-Iriepa, Daniel, Oset-Gasque, Maria-Jesus, Marco-Contelles, Jose, Musilek, Kamil, Ismaili, Lhassane
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.01.2019
• Subjects: Biochemistry & Molecular Biology; Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; ORAC; MONOAMINE-OXIDASE; BUTYRYLCHOLINESTERASE; TARGET-DIRECTED LIGANDS; MAO-B; Antioxidant; AMYLOID PEPTIDE; MAO-A; cholinesterases; donepezil; POTENTIAL TREATMENT; PH; UPDATE; MAO; Ugi-4MCR; CHOLINESTERASE/MONOAMINE OXIDASE-INHIBITORS; PHARMACOLOGICAL EVALUATION
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2018.1545766

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 mu M), hMAO A (IC50 = 2.78 +/- 0.12 mu M), and MAO B (IC50 = 21.29 +/- 3.85 mu 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. [GRAPHICS] .