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

Research output: Contribution to journalArticle

10 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

Fingerprint

Methicillin-Resistant Staphylococcus aureus
Benzene
Derivatives
Hydroxyl Radical
Molecules
Methicillin
Molecular dynamics
Molecular Dynamics Simulation
Structure-Activity Relationship
Computer simulation
Pharmacology

Keywords

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

ASJC Scopus subject areas

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

Cite this

Sawada, H., Onoda, K., Morita, D., Ishitsubo, E., Matsuno, K., Tokiwa, H., ... 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

Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives. / Sawada, Hiromi; Onoda, Kenji; Morita, Daichi; Ishitsubo, Erika; Matsuno, Kenji; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 24, 15.12.2013, p. 6563-6568.

Research output: Contribution to journalArticle

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, vol. 23, no. 24, pp. 6563-6568. https://doi.org/10.1016/j.bmcl.2013.10.069
Sawada, Hiromi ; Onoda, Kenji ; Morita, Daichi ; Ishitsubo, Erika ; Matsuno, Kenji ; Tokiwa, Hiroaki ; Kuroda, Teruo ; Miyachi, Hiroyuki. / Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 24. pp. 6563-6568.
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