Document Report Card

ID: ALA1146231

Journal: J Med Chem

Title: Novel semisynthetic derivative of antibiotic Eremomycin active against drug-resistant gram-positive pathogens including Bacillus anthracis.

Authors: Maples KR, Wheeler C, Ip E, Plattner JJ, Chu D, Zhang YK, Preobrazhenskaya MN, Printsevskaya SS, Solovieva SE, Olsufyeva EN, Heine H, Lovchik J, Lyons CR.

Abstract: Five adamantyl-containing carboxamides of eremomycin or vancomycin were synthesized and their antibacterial activities against some Gram-positive clinical isolates were investigated in vitro and in vivo. The adamantyl-2 amide of glycopeptide antibiotic eremomycin (1a in Chart 1, AN0900) was the most active compound and showed high activity against several Gram-positive pathogens: vancomycin-susceptible staphylococci and enterococci, glycopeptide-intermediate-resistant Staphylococcus aureus, and glycopeptide-resistant enterococci. Compound 1a was equally active in vitro against both Ciprofloxacin-susceptible and -resistant Bacillus anthracis strains (MICs 0.25-0.5 microg/mL). It was distinguished by having a 2.8 h half-life (t1/2) in mice and a volume of distribution of 2.18 L/kg. Compound 1a was active against Staphylococcus aureus in mice (iv) and provided complete protection against a lethal intravenous challenge with vegetative B. anthracis bacilli and also in a murine pulmonary anthrax model in which mice were challenged with Bacillus anthracis spores.

CiteXplore: 17608397

DOI: 10.1021/jm0700058