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Please use this identifier to cite or link to this item: http://acervodigital.unesp.br/handle/11449/26090
Title: 
Molecular Docking and Molecular Dynamic Studies of Semi-Synthetic Piperidine Alkaloids as Acetylcholinesterase Inhibitors
Author(s): 
Institution: 
  • Universidade Estadual Paulista (UNESP)
  • Universidade Federal do Rio de Janeiro (UFRJ)
  • Universidade Federal do Rio Grande do Sul (UFRGS)
  • Universidade Federal de Alfenas (UNIFAL)
ISSN: 
0103-5053
Sponsorship: 
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
  • Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Sponsorship Process Number: 
FAPESP: 03/02176-7
Abstract: 
The mixture of semi-synthetic derivatives (-)-3-O-acetyl-cassine hydrochloride and (-)-3-O-acetyl-spectaline hydrochloride, prepared from the mixture of natural alkaloids (-)-cassine and (-)-spectaline (4:1) isolated from Senna spectabilis, has been shown to be a potent acetylcholinesterase (AChE) inhibitor, thereby prompting further molecular studies. In this sense, docking and dynamic molecular studies were carried out in this work, aiming to acquire a deeper understanding about all the structural aspects of molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides, which differ with respect to their AChE inhibitory potentials. Both molecules establish important interactions with the peripheral anionic site within the catalytic gorge of Torpedo californica AChE. However, only the major compound (-)-3-O-acetyl-cassine hydrochloride significantly interacts with the catalytic triad. Explicit-solvent molecular dynamic simulations were conducted in order to gain better understanding about the hypothetical interactions taking place between the semi-synthetic alkaloid molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides and AChE. The data obtained in this study indicated that (-)-3-O-acetyl-cassine hydrochloride is the most potent inhibitor of AChE possibly due to the favorable interactions of this molecule with the target protein, with lower desolvation cost. These results suggested that the size of the side chain has an effect on the inhibitory potential of the evaluated molecules and may represent the starting point for the development of new derivatives of (-)-3-O-acetyl-cassine hydrochloride, with a view to the discovery of new effective AChE inhibitors.
Issue Date: 
1-Jan-2012
Citation: 
Journal of The Brazilian Chemical Society. São Paulo: Soc Brasileira Quimica, v. 23, n. 1, p. 163-U505, 2012.
Time Duration: 
163-U505
Publisher: 
Soc Brasileira Quimica
Keywords: 
  • molecular docking
  • molecular dynamic
  • piperidine alkaloids
  • acetylcholinesterase inhibitors
Source: 
http://dx.doi.org/10.1590/S0103-50532012000100023
URI: 
Access Rights: 
Acesso aberto
Type: 
outro
Source:
http://repositorio.unesp.br/handle/11449/26090
Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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