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 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).

Palabras clave: Steroids , Neurosteroids , Γ-Aminobutyric Acid , Gaba , Gabaa Receptor

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Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)

Identificadores

URI: http://hdl.handle.net/11336/30976

DOI: http://dx.doi.org/10.1016/j.bmc.2008.01.048

URL: http://www.sciencedirect.com/science/article/pii/S0968089608000680

Colecciones

Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)

Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS

Articulos(UMYMFOR)
Articulos de UNID.MICROANAL.Y MET.FISICOS EN QUIM.ORG.(I)

Citación

Burton, Gerardo; Coirini, Hector; Edelsztein, Valeria Carolina; Garland, María T.; Baggio, Ricardo Fortunato; Veleiro, Adriana Silvia; et al.; Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs; Elsevier; Bioorganic & Medicinal Chemistry; 16; 7; 1-2008; 3831-3838

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