In Vivo Activity of LCB 01-0699, a Prodrug of LCB 01-0648, against Staphylococcus aureus

Abstract

LCB01-0648 is a novel oxazolidinone compound that shows potent antibacterial activities against most Gram-positive cocci, including the multi-drug resistant Staphylococcus aureus. In this study, in vivo activity of LCB01-0699, a LCB01-0648 prodrug, against S. aureus was evaluated in comparison with that of Linezolid. The results of the systemic infection study demonstrated that LCB01-0699 was more potent than Linezolid against methicillin-susceptible and -resistant S. aureus strains. The in vivo efficacy of LCB01-0699 against methicillin-susceptible and -resistant S. aureus strains in a skin infection model showed more potent activity than Linezolid. LCB01-0699 shows potent in vivo activity against methicillin-susceptible and -resistant S. aureus strains, suggesting that LCB01-0699 would be a novel candidate for the treatment of these infectious diseases caused by S. aureus.

Oxazolidinones as versatile scaffolds in medicinal chemistry

“…LegoChem Biosciences, Inc. (Daejeon, South Korea) has developed several oxazolidinone derivatives as antibacterial agents in the last decade. 32–35 For example, compound 13 (LCB01-0062) (Fig. 2) showed in vitro activity against clinical isolates of Gram-positive bacteria compared to several antibacterial drugs, including linezolid, erythromycin, ciprofloxacin, and vancomycin.…”

“…2 ). 32 Pharmacokinetic (PK) studies in a rat model demonstrated that most of compound 15 was converted to the parent compound 14. The AUC last (area under the concentration–time curve from time zero to the last sampling time) of compound 15 was found to be 5.08 mg h L −1 whilst the AUC last of compound 14 was 85.0 mg h L −1 .…”

“…Furthermore, it did not show any change in reticulocyte count, suggesting that it was not associated with myelosuppression. 32 …”