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

被引:9
作者
Kappenberg, Yuri G. [1 ]
Nogara, Pablo A. [2 ,3 ]
Stefanello, Felipe S. [1 ]
Delgado, Cassia P. [2 ]
Rocha, Joao B. T. [2 ]
Zanatta, Nilo [1 ]
Martins, Marcos A. P. [1 ]
Bonacorso, Helio G. [1 ]
机构
[1] Univ Fed Santa Maria, Dept Quim, Nucleo Quim Heterociclos NUQUIMHE, BR-97105900 Santa Maria, RS, Brazil
[2] Univ Fed Santa Maria, Dept Bioquim & Biol Mol, BR-97105900 Santa Maria, RS, Brazil
[3] Inst Fed Sul Rio Grandense IFSul, BR-96418400 Bage, RS, Brazil
关键词
Tacrine; 3-Triazoles; Triazolopyridines; Aminoquinolines; Benzoquinolines; Cholinesterase inhibition; Enzymatic activity; Molecular docking; MICROWAVE-ASSISTED SYNTHESIS; BIOLOGICAL EVALUATION; DIRECTED LIGANDS; ANALOGS; DERIVATIVES; AGENTS; OPTIMIZATION; SELENOPHENE; ANTIFUNGAL; PARAMETERS;
D O I
10.1016/j.bioorg.2023.106704
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An efficient [4 + 2] cyclization protocol to synthesize a series of twelve examples of 1,2,3-triazolo[4,5-b]ami-noquinolines (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 (IC50 = 12.01 mu M), while 5ib from 3-sulfonamido-carbonitrile (3i) was the most significant in-hibitor for BChE (IC50 = 1.78 mu M). 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.
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页数:15
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