Preliminary structure-activity relationship on theonellasterol, a new chemotype of FXR antagonist, from the marine sponge Theonella swinhoei.
Mar Drugs
; 10(11): 2448-66, 2012 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-23203270
ABSTRACT
Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esteroles
/
Receptores Citoplasmáticos y Nucleares
/
Theonella
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mar Drugs
Asunto de la revista:
BIOLOGIA
/
FARMACOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Italia