title: Synthesis of tetrazole analogues of phosphonohydroxamic acids: an attempt to improve the inhibitory activity against the DXR.
abstract: This work is focused on the design of new antimicrobial drugs and on the development of lipophilic inhibitors of the DXR, the second enzyme of the MEP pathway for the biosynthesis of isoprene units in most bacteria, by replacing the phosphonate group of fosmidomycin derivatives by a tetrazoyl moiety capable of multiple hydrogen bonding. The N- and C-substituted tetrazole analogues of phosphonohydroxamate inhibitors were synthesized and tested on the DXR of Escherichia coli. This work points out the hypothesis that the phosphonate/phosphate recognition site might be too rigid to accommodate other functional groups.
authors: Université de Strasbourg, CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France.
authors: Anh Thu
authors: AT
authors: Nguyen-Trung
authors: Denis
authors: D
authors: Tritsch
authors: Catherine
authors: C
authors: Grosdemange-Billiard
authors: Michel
authors: M
authors: Rohmer
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005578:Fosfomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D029968:Escherichia coli Proteins; D006877:Hydroxamic Acids; D009097:Multienzyme Complexes; D013777:Tetrazoles; C045574:1H-tetrazole; D005578:Fosfomycin; C024640:fosmidomycin