Structural requirements of salicylanilides for uncoupling activity in mitochondria: quantitative analysis of structure-uncoupling relationships.
Biochim Biophys Acta
; 936(3): 504-12, 1988 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-3196713
ABSTRACT
The uncoupling activities of more than 20 salicylanilides were measured in rat liver mitochondria. The activities, expressed as the minimum concentrations required for full release of state-4 respiration, ranged over three orders of magnitude. The acid dissociation constant, pKA, and the partition coefficient between octanol and water (Poct) of some of the salicylanilides were determined. These two parameters were found to be well expressed in terms of the Hammett constant, sigma, and the hydrophobic substituent coefficient, II, respectively. The pKA and log Poct values of all the salicylanilides were predicted according to these relationships. Furthermore, the capacity factor, k', on high-performance liquid chromatography was determined on glyceryl-coated-controlled pore glass (gly-CPG). Values of log k' correlated well with those of log Poct. The uncoupling activities of the salicylanilides were analyzed in terms of these three parameters. Both hydrophobic and electron-withdrawing properties were found to be essential for induction of potent uncoupling activity. The correlations using log k' were better than those using log Poct.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
/
Salicilanilidas
/
Desacopladores
/
Mitocôndrias Hepáticas
/
Salicilamidas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
1988
Tipo de documento:
Article
País de afiliação:
Japão