Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives

Rastegari, A. and Nadri, H. and Mahdavi, M. and Moradi, A. and Mirfazli, S.S. and Edraki, N. and Moghadam, F.H. and Larijani, B. and Akbarzadeh, T. and Saeedi, M. (2019) Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives. Bioorganic Chemistry, 83. pp. 391-401.

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Abstract

Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC50 = 1.80 µM), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC50 = 21.13 µM confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against H2O2-induced cell death in PC12 neurons at 50 µM as well as metal chelating ability toward Fe2+, Cu2+, and Zn2+ ions. © 2018 Elsevier Inc.

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