Synthesis and biological evaluation of aryl phosphoramidate prodrugs of fosfoxacin and its derivatives.


Catherine Grosdemange-Billiard


Laboratoire Chimie et Biochimie de Molécules Bioactives - Université de Strasbourg/CNRS, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France. Electronic address: [Email]


Aryl phosphoramidate prodrugs of fosfoxacin derivatives 15a-b and 8a-b were synthesized and investigated for their ability to target bacteria. No growth inhibition was observed neither for Mycobacterium smegmatis nor for Escherichia coli on solid medium, demonstrating the absence of release of the active compounds in the bacterial cells. Investigation of the stability of the prodrugs and their multienzymatic cleavage in abiotic and biotic conditions showed that the use of aryl phosphoramidate prodrug approach to deliver non-nucleotides compounds is not obvious and might not be appropriate for an antimicrobial drug.


Antimicrobials,DXR,MEP pathway,Mycobacterium tuberculosis,Phosphate prodrug,