TY - JOUR
T1 - Novel-substituted heterocyclic GABA analogues. Enzymatic activity against the GABA-AT enzyme from pseudomonas fluorescens and in silico molecular modeling
AU - Tovar-Gudi o, Erika
AU - Guevara-Salazar, Juan Alberto
AU - Bahena-Herrera, José Raúl
AU - Trujillo-Ferrara, José Guadalupe
AU - Martínez-Campos, Zuleyma
AU - Razo-Hernandez, Rodrigo Said
AU - Santiago, Ángel
AU - Pastor, Nina
AU - Fernandez-Zertuche, Mario
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - GABA-AT docking
KW - GABA-AT inhibitors
KW - Heterocyclic GABA analogues
KW - Molecular electrostatic potential
UR - http://www.scopus.com/inward/record.url?scp=85047200156&partnerID=8YFLogxK
U2 - 10.3390/molecules23051128
DO - 10.3390/molecules23051128
M3 - Artículo
C2 - 29747438
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 5
M1 - 1128
ER -