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

Abstract

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 Salmonella, Pseudomonas aeruginosa, and Listeria.

Phosphonopeptides containing free phosphonic groups: recent advances

“…4). 33,34 Since the introduction of nonproteinogenic amino acids into peptide chain usually inhibits or slower its hydrolysis these compounds have a chance to be more stable in body uids.…”

Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance

“…In the period subsequent to the work disclosed within this paper we performed systematic modifications to the structures of the inhibitors with this other goal in mind. The results of these subsequent investigations form the basis of our second and third papers which may be found within this Special Issue of molecules dedicated to microbial detection and identification [27,28].…”