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. 2010 Jun 2;1(6):258-62.
doi: 10.1021/ml100057z. eCollection 2010 Sep 9.

Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria

Tetsuya Tanino  1 , Satoshi Ichikawa  1 , Bayan Al-Dabbagh  2 , Ahmed Bouhss  2 , Hiroshi Oyama  3 , Akira Matsuda  1
Affiliations

Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria

Tetsuya Tanino et al. ACS Med Chem Lett. .

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.

Keywords: Antibiotics; MraY; Ugi four-component reaction; drug resistance; muraymycin; peptidoglycan.

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Figures

Figure 1
Figure 1
Structures of MRYs (1).
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
See this image and copyright information in PMC

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