67808-31-5Relevant articles and documents
DNA binding ligands targeting drug-resistant bacteria: Structure, activity, and pharmacology
Kaizerman, Jacob A.,Gross, Matthew I.,Ge, Yigong,White, Sarah,Hu, Wenhao,Duan, Jian-Xin,Baird, Eldon E.,Johnson, Kirk W.,Tanaka, Richard D.,Moser, Heinz E.,Bürli, Roland W.
, p. 3914 - 3929 (2007/10/03)
We describe the lead optimization and structure-activity relationship of DNA minor-groove binding ligands, a novel class of antibacterial molecules. These compounds have been shown to target A/T-rich sites within the bacterial genome and, as a result, inhibit DNA replication and RNA transcription. The optimization was focused on N-terminal aromatic heterocycles and C-terminal amines and resulted in compounds with improved in vivo tolerability and excellent in vitro antibacterial potency (MIC ≥ 0.031 μg/mL) against a broad range of Gram-positive pathogens, including drug-resistant strains such as methicillin-resistant Stapylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant Enterococcus faecalis (VRE). In a first proof-of-concept study, a selected compound (35) showed in vivo efficacy in a mouse peritonitis model against methicillin-sensitive S. aureus infection with an ED50 value of 30 mg/kg.
