title: 4-Pyridone derivatives as new inhibitors of bacterial enoyl-ACP reductase FabI.
abstract: Bacterial FAS provides essential fatty acids for use in the assembly of key cellular components. Among them, FabI is an enoyl-ACP reductase which catalyzes the final and rate-limiting step of bacterial FAS. It is a potential target for selective antibacterial action, because it shows low overall sequence homology with mammalian enzymes. Until today, various compounds have been reported as inhibitors of bacterial FabI-inhibitory compounds. To discover novel small-molecular FabI inhibitors, we initially screened our compound library for inhibitory activity toward FabI of Escherichia coli. And discovered 4-pyridone derivatives as a lead compound. Structure optimization studies yielded 4-pyridone derivatives 7n having strong FabI-inhibitory and antibacterial activities against Staphylococcus aureus. There have been no reports concerning 4-pyridone derivatives as FabI inhibitor.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Ko
authors.initials: K
authors.lastname: Kumura
authors.forename: Sho
authors.initials: S
authors.lastname: Takahata
authors.forename: Maiko
authors.initials: M
authors.lastname: Iida
authors.forename: Kunio
authors.initials: K
authors.lastname: Atsumi
mesh_terms: D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D011728:Pyridones; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)