Phenylimidazole derivatives as specific inhibitors of bacterial enoyl-acyl carrier protein reductase FabK

Tomohiro Ozawa; Hideo Kitagawa; Yasuo Yamamoto; Sho Takahata; Maiko Iida; Yumi Osaki; Keiko Yamada

doi:10.1016/j.bmc.2007.08.050

Phenylimidazole derivatives as specific inhibitors of bacterial enoyl-acyl carrier protein reductase FabK

Bioorg Med Chem. 2007 Dec 1;15(23):7325-36. doi: 10.1016/j.bmc.2007.08.050. Epub 2007 Sep 4.

Authors

Tomohiro Ozawa¹, Hideo Kitagawa, Yasuo Yamamoto, Sho Takahata, Maiko Iida, Yumi Osaki, Keiko Yamada

Affiliation

¹ Medicinal Chemistry Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.

PMID: 17892940
DOI: 10.1016/j.bmc.2007.08.050

Abstract

Bacterial enoyl-acyl carrier protein (ACP) reductases (FabI and FabK) catalyze the final step in each cycle of bacterial fatty acid biosynthesis and are attractive targets for the development of new antibacterial agents. Here, we report the development of novel FabK inhibitors with antibacterial activity against Streptococcus pneumoniae. Based on structure-activity relationship (SAR) studies of our screening hits, we have developed novel phenylimidazole derivatives as potent FabK inhibitors.

MeSH terms

Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Escherichia coli / enzymology
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry
Imidazoles / pharmacology*
K562 Cells
Microbial Sensitivity Tests
Molecular Structure
Stereoisomerism
Streptococcus pneumoniae / drug effects*
Streptococcus pneumoniae / enzymology*
Structure-Activity Relationship
Toxicity Tests

Substances

Enzyme Inhibitors
Imidazoles
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)