Synthesis of Albicidin Derivatives: Assessing the Role of N‐terminal Acylation on the Antibacterial Activity. (21st July 2016)

• Record Type: Journal Article
• Authors: Kerwat, Dennis; Grätz, Stefan; Kretz, Julian; Seidel, Maria; Kunert, Maria; Weston, John B.; Süssmuth, Roderich D.
• Is Part Of: ChemMedChem. Volume 11:Number 17(2016)
• Page Start: 1899
• Page End: 1903
• Publication Date: 2016-07-21
• Subjects: albicidin -- antibacterials -- antibiotics -- gyrase -- para-aminobenzoic acid -- peptides; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600231
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium, Xanthomonas albilineans, represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram‐positive and Gram‐negative microorganisms. Its unique structure potentially represents a new lead structure for the development of an antibacterial drug. Here we report the synthesis of 14 albicidin derivatives with structural variations at the N‐terminus, primarily investigating the effects of variation of cinnamoyl, phenylpropanoyl, and benzoyl residues. Gyrase inhibition in vitro and determination of minimal inhibitory concentrations were assessed in parallel. Activities in a nanomolar range and the importance of N‐acylation were demonstrated. Abstract : Advantages of acylated albicidin : The peptide antibiotic albicidin represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram‐positive and Gram‐negative microorganisms. 14 newly synthesized albicidin derivatives with structural variations at the N‐terminus are reported here. Gyrase inhibition and determination of minimal inhibitorial concentrations were assessed in parallel to show activities in a nm range and the necessity of N‐acylation.