Synthesis and Antimicrobial Activity of Phosphonopeptide Derivatives Incorporating Single and Dual Inhibitors

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 7; p. 1557
• Main Authors: Ng, Keng Tiong, Perry, John D, Marrs, Emma C L, Orenga, Sylvain, Anderson, Rosaleen J, Gray, Mark
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.03.2020; MDPI
• Subjects: Alanine; Amino acids; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - pharmacology; Antibiotics; Antimicrobial activity; Antimicrobial agents; Bacteria; Bacteria - drug effects; bacterial detection; beta-Alanine - analogs & derivatives; beta-Alanine - chemistry; Chemistry Techniques, Synthetic; Culture media; Diagnostic systems; Drug resistance; Enzymes; fosfalin; Gram-positive bacteria; Inhibitors; L-Alanine; Listeria; Microbial Sensitivity Tests; Microbiology; Molecular Structure; Pathogens; Peptides; Phosphopeptides - chemical synthesis; Phosphopeptides - pharmacology; Pseudomonas aeruginosa; Salmonella; Substrate inhibition; Substrates; Suicide; Suicide substrates; β-chloroalanine; bacterial detection; suicide substrates; β-chloroalanine; fosfalin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25071557

In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of "suicide substrates" that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on d/l-fosfalin and β-chloro-l-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including , , and .