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ACS Med Chem Lett. 2014 Mar 6;5(5):556-60. doi: 10.1021/ml5000096. eCollection 2014 May 8.

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa.

Author information

1
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., LTD. , Kita-21, Nishi-11 Kita-ku, Sapporo 001-0021, Japan.
2
Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
3
Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan ; Center for Research and Education on Drug Discovery, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

Abstract

It is urgent to develop novel anti-Pseudomonas agents that should also be active against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum of muraymycins toward P. aeruginosa was investigated by the systematic structure-activity relationship study. It was revealed that two functional groups, a lipophilic side chain and a guanidino group, at the accessory moiety of muraymycins were important for the anti-Pseudomonas activity, and analogue 29 exhibited antibacterial activity against a range of P. aeruginosa strains with the minimum inhibitory concentration values of 4-8 μg/mL.

KEYWORDS:

Antibiotics; MraY; anti-Pseudomonas; drug-resistance; muraymycin; peptidoglycan

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