title: N'-(alpha-aminoacyl)- and N'-alpha-(N-alkylamino)acyl derivatives of vancomycin and eremomycin. II. Antibacterial activity of N'-(alpha-aminoacyl)- and N'-alpha-(N-alkylamino)acyl derivatives of vancomycin and eremomycin.
abstract: The antibacterial activities of the series of novel N'-(alpha-aminoacyl)- and N'-alpha-(N-akylamino)acyl derivatives of eremomycin and vancomycin containing hydrophobic moieties have been investigated. The N'-(N-alkylglycyl) derivatives of vancomycin are more active against vancomycin-susceptible staphylococci and enterococci and glycopeptide intermediate-resistant Staphylococcus aureus (GISA) than the corresponding eremomycin derivatives, but except for N'-[N-(p-octyloxybenzyl)glycyl-vancomycin] (28) and N'-[N-(p-octyloxybenzyl)-L-alanyl-vancomycin (33)--they are less active against glycopeptide-resistant enterococci (GRE). Derivatives 28 and 33 are the most active compounds (MIC's for glycopeptide-sensitive staphylococci and enterococci are 0.25 approximately 1 microg/ml, for GISA 1 approximately 2 microg/ml, for GRE 2 approximately 6 microg/ml). In in vivo studies, derivative 28 was active against S. aureus infections in mice with ED(50) 1 mg/kg versus 2 mg/kg for vancomycin (iv). In general N'-(N-alkylglycyl)-derivatives of vancomycin and eremomycin were more active than the corresponding N'-aminoacylated derivatives of these antibiotics containing other than glycin amino acids (L-Lys, L-Met, L-Orn, L- and D-Ala) and also L- and D-Phe or benzyl-O-L-Tyr.
authors: Chiron Corporation, Emeryville, CA 94608, USA.
authors: Jake J
authors: JJ
authors: Plattner
authors: Daniel
authors: D
authors: Chu
authors: Elena P
authors: EP
authors: Mirchink
authors: Elena B
authors: EB
authors: Isakova
authors: Maria N
authors: MN
authors: Preobrazhenskaya
authors: Evgenia N
authors: EN
authors: Olsufyeva
authors: Olga V
authors: OV
authors: Miroshnikova
authors: Svetlana S
authors: SS
authors: Printsevskaya
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006020:Glycopeptides / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C053759:eremomycin; D014640:Vancomycin