Medicinal Chemistry Optimization of Acyldepsipeptides of the Enopeptin Class Antibiotics

• Published in: ChemMedChem Vol. 1; no. 7; pp. 689 - 693
• Main Authors: Hinzen, Berthold, Raddatz, Siegfried, Paulsen, Holger, Lampe, Thomas, Schumacher, Andreas, Häbich, Dieter, Hellwig, Veronica, Benet-Buchholz, Jordi, Endermann, Rainer, Labischinski, Harald, Brötz-Oesterhelt, Heike
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 10.07.2006; WILEY‐VCH Verlag
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibiotics; Bacillus subtilis - drug effects; Bacillus subtilis - ultrastructure; Chemistry, Pharmaceutical; Crystallography, X-Ray; drug resistance; Gram-positive bacteria; Gram-Positive Bacteria - drug effects; Gram-Positive Bacterial Infections - drug therapy; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; structure-activity relationships
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.200600055

The therapy of life‐threatening infections is significantly weakened by the global spread of antibiotic resistance. Synthetic exploration of enopeptin type acyldepsipeptide antibiotics revealed a remarkable structure–activity relationship. New compounds with improved in vitro antibiotic activity against Gram‐positive pathogens (including multiresistant strains) and in vivo activity in mouse models of lethal infection are described.