Design, synthesis and bioactions of novel stable mimetics of lipoxins and aspirin-triggered lipoxins.
Prostaglandins Leukot Essent Fatty Acids
; 73(3-4): 301-21, 2005.
Article
en En
| MEDLINE
| ID: mdl-16098719
The lipoxins (LX) are a class of potent endogenous oxygenated products that are enzymatically generated from arachidonic acid and have novel anti-inflammatory properties and promote resolution. Elucidation of the biochemical pathways involved in the metabolic inactivation of LX and the discovery of the aspirin-triggered lipoxins (ATL) provided the basis for the design and synthesis of stable analogs of LX and ATL. This special issue review describes the efforts that led to the design and synthesis of stable LX/ATL mimetics, which permitted the detailed elucidation of their novel biological roles, leading to the development of new anti-inflammatory agents that mimic their actions. These synthetic molecules provided the means to uncover the physiologic roles of both the LX and the ATL biosynthetic pathways which led to several unexpected discoveries. Among these findings is the involvement of polyisoprenyl phosphates (PIPP) in intracellular signaling mediated by presqualene diphosphate (PSDP), and the recognition of the novel roles of these lipid mediators in regulating cell trafficking during inflammation as well as in promoting resolution of inflammatory processes. These efforts also provided the basis for examining the potential therapeutic role of LX/ATL stable mimetics and led to the development of new analogs with improved pharmacokinetics that opened the way to potentially new approaches to treating human diseases.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Lipoxinas
/
Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Prostaglandins Leukot Essent Fatty Acids
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido