title: Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria.
abstract: Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b-e and 8b-e exhibited good activity against a range of Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure-activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on muraymycins.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanino
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
authors.affiliation: Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619 CNRS, Université Paris-Sud, Bât. 430, Orsay F-91405, France.
authors.forename: Bayan
authors.initials: B
authors.lastname: Al-Dabbagh
authors.affiliation: Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619 CNRS, Université Paris-Sud, Bât. 430, Orsay F-91405, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bouhss
authors.affiliation: Shionogi Innovation Center for Drug Discovery, Shionogi & Co., LTD., Kita-21, Nishi-11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
keywords: Antibiotics; MraY; Ugi four-component reaction; drug resistance; muraymycin; peptidoglycan