1,2,3-Triazolo[4,5-b]aminoquinolines: Design, synthesis, structure, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and molecular docking of novel modified tacrines.

Autor: Kappenberg YG; Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil., Nogara PA; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, 97105-900 - Santa Maria, RS, Brazil; Instituto Federal Sul-Rio-Grandense (IFSul), 96418-400- Bagé, RS, Brazil., Stefanello FS; Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil., Delgado CP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, 97105-900 - Santa Maria, RS, Brazil., Rocha JBT; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, 97105-900 - Santa Maria, RS, Brazil., Zanatta N; Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil., Martins MAP; Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil., Bonacorso HG; Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil. Electronic address: helio.bonacorso@ufsm.br.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 Oct; Vol. 139, pp. 106704. Date of Electronic Publication: 2023 Jul 06.
DOI: 10.1016/j.bioorg.2023.106704
Abstrakt: An efficient [4 + 2] cyclization protocol to synthesize a series of twelve examples of 1,2,3-triazolo[4,5-b]aminoquinolines (5) as novel structurally modified tacrines was obtained by reacting readily accessible precursors (i.e., 3-alky(aryl)-5-amino-1,2,3-triazole-4-carbonitriles (3)) and selected cycloalkanones (4) of five-, six-, and seven-membered rings. We evaluated the AChE and BChE inhibitory activity of the novel modified tacrines 5, and the compound derivatives from cyclohexanone (4b) showed the best AChE and BChE inhibitory activities. Specifically, 1,2,3-triazolo[4,5-b]aminoquinolines 5bb obtained from 3-methyl-carbonitrile (3b) showed the highest AChE (IC 50  = 12.01 μM), while 5ib from 3-sulfonamido-carbonitrile (3i) was the most significant inhibitor for BChE (IC 50  = 1.78 μM). In general, the inhibitory potency of compound 5 was weaker than the pure tacrine reference, and our findings may help to design and develop novel anticholinesterase drugs based on modified tacrines.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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