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

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa

Yusuke Takeoka  1 , Tetsuya Tanino  2 , Mitsuaki Sekiguchi  1 , Shuji Yonezawa  1 , Masahiro Sakagami  1 , Fumiyo Takahashi  1 , Hiroko Togame  1 , Yoshikazu Tanaka  1 , Hiroshi Takemoto  1 , Satoshi Ichikawa  3 , Akira Matsuda  2
Affiliations

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa

Yusuke Takeoka et al. ACS Med Chem Lett. .

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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Figures

Figure 1
Figure 1
Structures and biological activity of muraymycin D2 and its lipophilic analogue.
Figure 2
Figure 2
Structures of muraymycin analogues.
Scheme 1
Scheme 1. Synthesis of Acyl Analogues 11–19
Figure 3
Figure 3
Molecular design of analogues 21–29.
Scheme 2
Scheme 2. Synthesis of Analogues 21–26
Scheme 3
Scheme 3. Synthesis of Branched Analogues 27–29
See this image and copyright information in PMC

References

    1. Tam V. H.; Chang K. T.; Abdelraouf K.; Brioso C. G.; Ameka M.; McCaskey L. A.; Weston J. S.; Caeiro J. P.; Garey K. W. Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2010, 54, 1160–1164. - PMC - PubMed
    1. Page M. G.; Heim J. Prospects for the next anti-Pseudomonas drug. Curr. Opin. Pharmacol. 2009, 9, 558–565. - PubMed
    1. Scheld M.; Spellberg B.; Bartlett J. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 48, 1–12. - PubMed
    1. Payne D. J.; Gwynn M. N.; Holms D. J.; Pompliano D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discovery 2007, 6, 29–40. - PubMed
    1. Talbot G. H.; Bradley J.; Edwards J. E. Jr.; Gilbert D.; Scheld M.; Bartlett J. G. Bad bugs need drugs: an update on the development pipeline from the antimicrobial availability task force of the Infectious Diseases Society of America. Clin. Infect. Dis. 2006, 42, 657–668. - PubMed

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