Intracellular targeting and pharmacological activity of the superoxide dismutase mimics MnTE-2-PyP5+ and MnTnHex-2-PyP5+ regulated by their porphyrin ring substituents.
Inorg Chem
; 52(8): 4121-3, 2013 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-23551184
ABSTRACT
Manganese porphyrin-based drugs are potent mimics of the enzyme superoxide dismutase. They exert remarkable efficacy in disease models and are entering clinical trials. Two lead compounds, MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+), have similar catalytic rates, but differ in their alkyl chain substituents (ethyl vs n-hexyl). Herein we demonstrate that these changes in ring substitution impact upon drug intracellular distribution and pharmacological mechanism, with MnTnHex-2-PyP(5+) superior in augmenting menadione toxicity. These findings establish that both catalytic activity and intracellular distribution determine drug action.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
/
Metaloporfirinas
/
Antioxidantes
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Inorg Chem
Año:
2013
Tipo del documento:
Article
País de afiliación:
Australia