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Structural optimization and antibacterial evaluation of rhodomyrtosone B analogues against MRSA strains

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections are well-known as a significant global health challenge. In this study, twenty-two congeners of the natural antibiotic rhodomyrtosone B (RDSB) were synthesized with the aim of specifically enhancing the structural diversity through modifying the pendant acyl moiety. The structure–activity relationship study against various MRSA strains revealed that a suitable hydrophobic acyl tail in the phloroglucinol scaffold is a prerequisite for antibacterial activity. Notably, RDSB analogue 11k was identified as a promising lead compound with significant in vitro and in vivo antibacterial activities against a panel of hospital mortality-relevant MRSA strains. Moreover, compound 11k possessed other potent advantages, including breadth of the antibacterial spectrum, rapidity of bactericidal action, and excellent membrane selectivity. The mode of action study of compound 11k at the biophysical and morphology levels disclosed that 11k exerted its MRSA bactericidal action by membrane superpolarization resulting in cell lysis and membrane disruption. Collectively, the presented results indicate that the novel modified RDSB analogue 11k warrants further exploration as a promising candidate for the treatment of MRSA infections.

Graphical abstract: Structural optimization and antibacterial evaluation of rhodomyrtosone B analogues against MRSA strains

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Publication details

The article was received on 17 May 2018, accepted on 09 Aug 2018 and first published on 07 Sep 2018


Article type: Research Article
DOI: 10.1039/C8MD00257F
Citation: Med. Chem. Commun., 2018, Advance Article
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    Structural optimization and antibacterial evaluation of rhodomyrtosone B analogues against MRSA strains

    L. Zhao, H. Liu, L. Huo, M. Wang, B. Yang, W. Zhang, Z. Xu, H. Tan and S. Qiu, Med. Chem. Commun., 2018, Advance Article , DOI: 10.1039/C8MD00257F

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