Synthesis and biological evaluation of aryl phosphoramidate prodrugs of fosfoxacin and its derivatives.
Fiche publication
Date publication
août 2019
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GROSDEMANGE-BILLIARD Catherine
Tous les auteurs :
Munier M, Tritsch D, Lièvremont D, Rohmer M, Grosdemange-Billiard C
Lien Pubmed
Résumé
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.
Mots clés
Antimicrobials, DXR, MEP pathway, Mycobacterium tuberculosis, Phosphate prodrug
Référence
Bioorg Chem. 2019 08;89:103012