Artículos de revistas
Combining The Pharmacophore Features Of Coumarins And 1,4-substituted 1,2,3-triazoles To Design New Acetylcholinesterase Inhibitors: Fast And Easy Generation Of 4-methylcoumarins/1,2,3-triazoles Conjugates Via Click Chemistry
Registro en:
Journal Of The Brazilian Chemical Society. Soc Brasileira Quimica, v. 27, p. 1541 - 1550, 2016.
0103-5053
1678-4790
WOS:000384585800004
10.5935/0103-5053.20160033
Autor
Torres
Fernando C.; Goncalves
Guilherme A.; Vanzolini
Kenia L.; Merlo
Aloir A.; Gauer
Bruna; Holzschuh
Maribete; Andrade
Saulo; Piedade
Maristela; Garcia
Solange C.; Carvalho
Ivone; von Poser
Gilsane L.; Kawano
Daniel F.; Eifler-Lima
Vera L.; Cass
Quezia B.
Institución
Resumen
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coumarins are a large class of compounds that display a range of interesting biological properties, being considered privileged structures because of the ability of their 2H-chromen-2-one nuclei to bind to multiple pharmacological targets. We hypothesized that the linkage of a second pharmacophore nucleus to the 2H-chromen-2-one core, the 1,2,3-triazole moiety, would entail more selective and pharmacologically active coumarins. Therefore, we describe the synthesis of fourteen 4-methylcoumarins/1,4-substituted 1,2,3-triazole conjugates, which were predicted by in silico methods to inhibit acetylcholinesterase (AChE) and proved to be moderate in vitro inhibitors of this enzyme. Molecular docking simulations suggest that the most active of these compounds has a putative binding mode similar to donepezil, both occupying the peripheral anionic site of AChE, which is associated with the secondary noncholinergic functions of the enzyme. This highlights the potential of this series for further optimization in the search of new coumarins for the treatment of Alzheimer's disease. 27 9 1541 1550 Brazilian funding agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Brazilian funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazilian funding agency Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) Brazilian funding agency Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Brazilian funding agency Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCT-IF) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)