α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues.

Aurore Dreneau,Michel Rohmer,Fanny S Krebs,Catherine Grosdemange-Billiard,Denis Tritsch,Mathilde Munier,Didier Lièvremont,Chheng Ngov

doi:10.3390/molecules26165111

Aurore Dreneau, Michel Rohmer + Show 6 more

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https://doi.org/10.3390/molecules26165111

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Abstract

Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on Escherichia coli. Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC50 in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against E. coli on Petri dishes in comparison with the corresponding phosphates and the non-fluorinated phosphonate.

Highlights

Antimicrobial resistance affecting anyone in any country is rising to dangerously high levels in all parts of the world and has been recognized as a global health crisis by the United Nations and the World Health Organization (WHO)
Prevention and Control (ECDPC) estimated that about 33,000 people died each year from an infection due to antimicrobial-resistant bacteria, frequently while receiving health care i.e., from nosocomial infections [2]
The key precursor has been prepared by a copper(I)

Summary

Introduction

Antimicrobial resistance affecting anyone in any country is rising to dangerously high levels in all parts of the world and has been recognized as a global health crisis by the United Nations and the World Health Organization (WHO). It is crucial and urgent to identify new targets in order to elaborate and develop new drugs. In this respect, the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the two precursors of all isoprenoids, via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is an attractive prospect. The biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the two precursors of all isoprenoids, via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is an attractive prospect This pathway is essential and present in many Gram-negative and Grampositive bacteria as well as protozoans, e.g., Plasmodium species responsible for malaria [3]

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