Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives

Hiromi Sawada, Kenji Onoda, Daichi Morita, Erika Ishitsubo, Kenji Matsuno, Hiroaki Tokiwa, Teruo Kuroda, Hiroyuki Miyachi

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12 Citations (Scopus)

Abstract

We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The structure-activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A-B-benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity.

Original languageEnglish
Pages (from-to)6563-6568
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number24
DOIs
Publication statusPublished - Dec 15 2013

Keywords

  • Isoplagiochin
  • Marchantin
  • Methicillin resistance
  • Riccardin
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Sawada, H., Onoda, K., Morita, D., Ishitsubo, E., Matsuno, K., Tokiwa, H., Kuroda, T., & Miyachi, H. (2013). Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives. Bioorganic and Medicinal Chemistry Letters, 23(24), 6563-6568. https://doi.org/10.1016/j.bmcl.2013.10.069