title: Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.
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.
authors.affiliation: Preclinical Research, F. Hoffmann-La Roche Ltd., CH-4070 Basle, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Apfel
authors.forename: D W
authors.initials: DW
authors.lastname: Banner
authors.forename: D
authors.initials: D
authors.lastname: Bur
authors.forename: M
authors.initials: M
authors.lastname: Dietz
authors.forename: T
authors.initials: T
authors.lastname: Hirata
authors.forename: C
authors.initials: C
authors.lastname: Hubschwerlen
authors.forename: H
authors.initials: H
authors.lastname: Locher
authors.forename: M G
authors.initials: MG
authors.lastname: Page
authors.forename: W
authors.initials: W
authors.lastname: Pirson
authors.forename: G
authors.initials: G
authors.lastname: Rossé
authors.forename: J L
authors.initials: JL
authors.lastname: Specklin
mesh_terms: D000581:Amidohydrolases; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016993:Chlamydophila pneumoniae / Q000187:drug effects; D018360:Crystallography, X-Ray; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006193:Haemophilus influenzae / Q000187:drug effects; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D001936:Moraxella catarrhalis / Q000187:drug effects; D009177:Mycoplasma pneumoniae / Q000187:drug effects; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012141:Respiratory Tract Infections / Q000382:microbiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase