Synthesis and biological evaluation of phosphate isosters of fosmidomycin and analogs as inhibitors of Escherichia coli and Mycobacterium smegmatis 1-deoxyxylulose 5-phosphate reductoisomerases.
Details
Serval ID
serval:BIB_D7A1B4F80190
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synthesis and biological evaluation of phosphate isosters of fosmidomycin and analogs as inhibitors of Escherichia coli and Mycobacterium smegmatis 1-deoxyxylulose 5-phosphate reductoisomerases.
Journal
Bioorganic & medicinal chemistry
ISSN
1464-3391 (Electronic)
ISSN-L
0968-0896
Publication state
Published
Issued date
15/01/2017
Peer-reviewed
Oui
Volume
25
Number
2
Pages
684-689
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Hydroxamate analogs of fosfoxacin, the phosphate homolog of fosmidomycin, have been synthesized and their activity tested on Escherichia coli and Mycobacterium smegmatis DXRs. Except for compound 4b, the IC <sub>50</sub> values of phosphate derivatives are approximately 10-fold higher than those of the corresponding phosphonates. Although their inhibitory activity on Escherichia coli DXR is less efficient than their phosphonate analogs, we report the ability of phosphate compounds to inhibit the growth of Escherichia coli. This work points out that the uptake of fosfoxacin and its analogs is taking place via the GlpT and UhpT transporters. As expected, these compounds are inefficient to inhibit the growth of M. smegmatis growth inhibition probably due to a lack of uptake.
Keywords
Aldose-Ketose Isomerases/antagonists & inhibitors, Aldose-Ketose Isomerases/metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors/chemical synthesis, Enzyme Inhibitors/chemistry, Enzyme Inhibitors/pharmacology, Escherichia coli/enzymology, Fosfomycin/analogs & derivatives, Fosfomycin/chemical synthesis, Fosfomycin/chemistry, Fosfomycin/pharmacology, Molecular Structure, Mycobacterium smegmatis/enzymology, Phosphates/chemistry, Phosphates/pharmacology, Structure-Activity Relationship, Antimicrobials, DXR, Fosfoxacin, Fosmidomycin, GlpT and UhpT transporters
Pubmed
Web of science
Create date
14/10/2024 9:10
Last modification date
15/10/2024 6:24