Phenothiazines as lipid peroxidation inhibitors and cytoprotective agents.
J Med Chem
; 35(4): 716-24, 1992 Feb 21.
Article
en En
| MEDLINE
| ID: mdl-1542098
A series of phenothiazines was synthesized and evaluated as in vitro inhibitors of iron-dependent lipid peroxidation. The MIC (minimum tested concentration that gave greater than or equal to 50% inhibition) for 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanolamine methanesulfonate (6) was 0.26 microM. Whereas methyl substitution at N-10 diminished activity nearly 100-fold, other structural modifications such as varying the amine group, the distance separating the amine substituent from the phenothiazine nucleus, and the linking group had little effect. Compound 6 was more effective than probucol, a known antioxidant, in blocking Cu2+ catalyzed oxidation of low-density lipoprotein (LDL) as measured by competitive scavenger receptor mediated degradation of 125I-labeled acetyl-LDL by mouse peritoneal macrophage cells in vitro. At a concentration of 5 microM, compound 6 also protected primary cultures of rat hippocampal neurons exposed to hydrogen peroxide (50 microM) when assessed 18 h later by fluorescein diacetate and propidium iodide uptake.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenotiazinas
/
Peroxidación de Lípido
/
Supervivencia Celular
/
Antioxidantes
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1992
Tipo del documento:
Article
Pais de publicación:
Estados Unidos