Novel-Substituted Heterocyclic GABA Analogues. Enzymatic Activity against the GABA-AT Enzyme from Pseudomonas fluorescens and In Silico Molecular Modeling.
Molecules
; 23(5)2018 05 09.
Article
en En
| MEDLINE
| ID: mdl-29747438
ABSTRACT
γ-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system, and a deficiency of GABA is associated with serious neurological disorders. Due to its low lipophilicity, there has been an intensive search for new molecules with increased lipophilicity to cross the blood-brain barrier to raise GABA concentrations. We have designed and evaluated in vitro and in silico some new analogues of GABA, where the nitrogen atom at the γ-position is embedded in heterocyclic scaffolds and determined their inhibitory potential over the GABA-AT enzyme from Pseudomonas fluorescens. These modifications lead to compounds with inhibitory activity as it occurs with compounds 18a and 19a. The construction of Pseudomonas fluorescens and human GABA-AT models were carried out by homology modeling. Docking assays were done for these compounds over the GABA-AT enzyme models where 19a showed a strong interaction with both GABA-AT enzymes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
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Pseudomonas fluorescens
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Modelos Moleculares
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Ácido gamma-Aminobutírico
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4-Aminobutirato Transaminasa
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Compuestos Heterocíclicos
Límite:
Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
México