Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease
Braz. j. pharm. sci
; 51(1): 53-61, Jan-Mar/2015. tab, graf
Article
en En
| LILACS
| ID: lil-751357
Biblioteca responsable:
BR1.1
ABSTRACT
Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.
RESUMO
A doença de Alzheimer (DA) é uma doença neurodegenerativado sistema nervoso central, em rápido crescimento, e antioxidantes ajudam a suprimir o estresse oxidativo causado por radicais livres, responsávies pela DA. Avaliou-se, biologicamente, série de derivados sintéticos de indol selecionados para identificar novos antioxidantes. A maioria dos compostos avaliados apresentou de significativa a boa propriedade antioxidante (valor de IC50 399,07140.0 ± 50 µM). Eftuaram-se estudos de Teoria do Funcional de Densidade (DFT) com os compostos e os seus correspondentes radicais livres. As diferenças de energia entre os compostos protótipos e os radicais livres correspondentes proporcionaram boa justificativa para a tendência encontrada nos seus valores de IC50. O ancoramento in silico dos compostos com a acetilcolinesterase (AChE) e com a butirilcolinesterase (BChE), que contribuem para a DA, foi, também, realizado para prever o seu potencial anti-DA.
Palabras clave
Acetilcolinesterase (AChE); Acetylcholinesterase (AChE); Alzheimer's disease; Ancoramento molecular; Antioxidant compounds; Butirilcolinesterase (BChE); Butyrylcholinesterase (BChE); Chronic diseases; Compostos antioxidantes; Computational studies; DPPH assay; Density Functional Theory; Derivados do indol; Doença de Alzheimer; Doenças crônicas; Ensaio de DPPH; Estudos computacionais; Indole derivatives; Molecular docking; Teoria do Funcional de Densidade
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1
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LILACS
Asunto principal:
Acetilcolinesterasa
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Butirilcolinesterasa
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Enfermedad de Alzheimer
Idioma:
En
Revista:
Braz. j. pharm. sci
Año:
2015
Tipo del documento:
Article
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Project document