Abstract
Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives have been synthesized and found to be potent inhibitors of Escherichia coli peptide deformylase (PDF). Most of the compounds synthesized and tested displayed antibacterial activities that cover several pathogens found in respiratory tract infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The potential of these compounds as antibacterial agents is discussed with respect to selectivity, intracellular concentrations in bacteria, and potential for resistance development.
MeSH terms
-
Amidohydrolases*
-
Aminopeptidases / antagonists & inhibitors*
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / metabolism
-
Anti-Bacterial Agents / pharmacology
-
Chlamydophila pneumoniae / drug effects
-
Crystallography, X-Ray
-
Drug Resistance, Microbial
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / metabolism
-
Enzyme Inhibitors / pharmacology
-
Escherichia coli / drug effects
-
Escherichia coli / enzymology
-
Escherichia coli / metabolism
-
Haemophilus influenzae / drug effects
-
Hydroxamic Acids / chemical synthesis*
-
Hydroxamic Acids / chemistry
-
Hydroxamic Acids / metabolism
-
Hydroxamic Acids / pharmacology
-
Models, Molecular
-
Moraxella catarrhalis / drug effects
-
Mycoplasma pneumoniae / drug effects
-
Protease Inhibitors / chemical synthesis
-
Protease Inhibitors / chemistry
-
Protease Inhibitors / metabolism
-
Protease Inhibitors / pharmacology
-
Respiratory Tract Infections / microbiology
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Anti-Bacterial Agents
-
Enzyme Inhibitors
-
Hydroxamic Acids
-
Protease Inhibitors
-
Aminopeptidases
-
Amidohydrolases
-
peptide deformylase