27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor

27-Nor-Δ4-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20β-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants and restored their norma...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., Pecci, A., Burton, G.
Formato: JOUR
Materias:
DAF-12 receptor Caenorhabditis elegans daf-9 Mutants Dafachronic acid Molecular dynamics
27 nor delta4 dafachronic acid
aldehyde
carboxylic acid derivative
cell nucleus receptor
cholesterol derivative
ligand
nuclear receptor DAF 12
unclassified drug
animal experiment
article
binding affinity
biological activity
Caenorhabditis elegans
controlled study
drug receptor binding
drug synthesis
in vitro study
in vivo study
ligand binding
molecular dynamics
molecular model
nonhuman
oxidative stress
phenotype
Animals
Caenorhabditis elegans Proteins
Cholestenes
Dose-Response Relationship, Drug
HEK293 Cells
Humans
Ligands
Models, Molecular
Molecular Conformation
Molecular Dynamics Simulation
Receptors, Cytoplasmic and Nuclear
Structure-Activity Relationship
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0960894X_v23_n10_p2893_Samaja
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:27-Nor-Δ4-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20β-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants and restored their normal resistance to oxidative stress. 27-Nor- Δ4-dafachronic acid was also able to directly bind and activate DAF-12 in a transactivation cell-based luciferase reporter assay, although it was less active than the corresponding 25R-and 25S dafachronic acids. The binding mode of the 27-Nor steroid was studied by molecular dynamics using a homology model of the CeDAF-12 receptor. © 2013 Elsevier Ltd. All rights reserved.

Ejemplares similares