DNA binding ligands targeting drug-resistant Gram-positive bacteria. Part 2: C-terminal benzimidazoles and derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 5; pp. 1259 - 1263
• Main Authors: Bürli, Roland W, Jones, Peter, McMinn, Dustin, Le, Quan, Duan, Jian-Xin, Kaizerman, Jacob A, Difuntorum, Stacey, Moser, Heinz E
• Format: Journal Article
• Language: English
• Published: England 08.03.2004
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Benzimidazoles - chemistry; Benzimidazoles - metabolism; Benzimidazoles - pharmacology; DNA - metabolism; Drug Delivery Systems - methods; Drug Resistance, Bacterial - physiology; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - metabolism; Ligands; Microbial Sensitivity Tests; Protein Binding - physiology
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2003.12.043

The synthesis and in vitro potency of DNA minor-groove binding antibacterials lacking the C-terminal amide bond are described. The crescent shaped molecules bear the positively charged amino group at an internal pyrrole unit instead of the C-terminus. Three structural parameters were investigated: the N-terminal unit, the internal amino group, and the C-terminal ring system. Several compounds demonstrated good in vitro potency against various Gram-positive bacteria and some molecules were moderately active against Escherichia coli, a representative Gram-negative strain.