Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activ...
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paper:paper_09680896_v16_n7_p3831_Alvarez2023-06-08T15:58:51Z Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs Alvarez, Lautaro Damián Veleiro, Adriana Silvia Edelsztein, Valeria Carolina Coirini, Héctor Burton, Gerardo γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1α,11α-Epoxypregnanolone (6) was more active than pregnanolone (2). © 2008 Elsevier Ltd. All rights reserved. Fil:Alvarez, L.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Edelsztein, V.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coirini, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v16_n7_p3831_Alvarez http://hdl.handle.net/20.500.12110/paper_09680896_v16_n7_p3831_Alvarez |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids |
spellingShingle |
γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Alvarez, Lautaro Damián Veleiro, Adriana Silvia Edelsztein, Valeria Carolina Coirini, Héctor Burton, Gerardo Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
topic_facet |
γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids |
description |
Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1α,11α-Epoxypregnanolone (6) was more active than pregnanolone (2). © 2008 Elsevier Ltd. All rights reserved. |
author |
Alvarez, Lautaro Damián Veleiro, Adriana Silvia Edelsztein, Valeria Carolina Coirini, Héctor Burton, Gerardo |
author_facet |
Alvarez, Lautaro Damián Veleiro, Adriana Silvia Edelsztein, Valeria Carolina Coirini, Héctor Burton, Gerardo |
author_sort |
Alvarez, Lautaro Damián |
title |
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
title_short |
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
title_full |
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
title_fullStr |
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
title_full_unstemmed |
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs |
title_sort |
synthesis and gabaa receptor activity of oxygen-bridged neurosteroid analogs |
publishDate |
2008 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v16_n7_p3831_Alvarez http://hdl.handle.net/20.500.12110/paper_09680896_v16_n7_p3831_Alvarez |
work_keys_str_mv |
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_version_ |
1768543286212952064 |