Phenothiazine Derivatives: The Importance of Stereoisomerism in the Tolerance and Efficacy of Antimicrobials.
Indian J Microbiol
; 64(2): 743-748, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-39010999
ABSTRACT
Stereoisomers are molecules that are identical in atomic constitution and bonding. The biological properties may, however, differ significantly between two enantiomers (individual stereoisomers). JBC 1847, a phenothiazine derivative with strong antimicrobial activity against Gram-positive bacteria, exists in two enantiomers, S and R. Under standard chemical synthesis (S)-and (R)-JBC 1847 will be present in 50/50 amount (racemic). In this study, we have investigated the antimicrobial activity, the in vivo tolerance and therapeutic efficacy of purified (S)-JBC 1847. Compared to JBC 1847 racemic, the antimicrobial activity of (S)-JBC 1847 in vitro was in the same range or slightly increased, while the maximum tolerable concentration in vivo was five times higher for (S)-JBC 1847 (5 mg/kg versus 20 mg/kg bodyweight). Furthermore, the in vivo efficacy of (S)-JBC 1847 in a mouse peritonitis MRSA model was comparable to the activity of vancomycin. In conclusion, the antimicrobial activity and tolerance of a medical stereoisomeric compound may be significantly different using purified enantiomers compared with the racemic state. Supplementary Information The online version contains supplementary material available at 10.1007/s12088-024-01309-3.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Indian J Microbiol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Dinamarca