Metabolism of small antimicrobial ß(2,2)-amino acid derivatives by murine liver microsomes.
Eur J Drug Metab Pharmacokinet
; 37(3): 191-201, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22383330
ABSTRACT
We have investigated the in vitro metabolism of three small antimicrobial ß(2,2)-amino acid derivatives (M (w) < 500) that are highly potent against methicillin resistant Staphylococcus aureus, and are among the first compounds designed from small cationic antimicrobial peptides with potential for oral administration. The ß(2,2)-amino acid derivatives are virtually completely resistant against degradation by proteases, and to further explore their drug potential, we have investigated the hepatic Phase I metabolism of this class of antimicrobial compounds. The ß(2,2)-amino acid derivatives were incubated with murine liver microsomes and the metabolites analyzed semi-quantitatively by HPLC-MS and qualitatively by ultra performance liquid chromatography coupled to a tandem mass spectrometer which enabled identification of the metabolites by careful interpretation of the collision activated dissociation spectra. The study shows that sterically hindered ß(2,2)-amino acid derivatives that otherwise are stable against proteolytic degradation underwent Phase I metabolism and were oxidized to a number of different metabolites depending on the structure of the ß(2,2)-amino acid side-chains.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Microsomas Hepáticos
/
Péptidos Catiónicos Antimicrobianos
Límite:
Animals
Idioma:
En
Revista:
Eur J Drug Metab Pharmacokinet
Año:
2012
Tipo del documento:
Article
País de afiliación:
Noruega