Minimum structural requirements for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s

详细信息    查看全文

• 作者：Kana Fujii ; Daichi Morita ; Kenji Onoda ; Teruo Kuroda ; Hiroyuki Miyachi ; ^{miyachi@pharm.okayama-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Macrocyclic bis(bibenzyl) derivative ; Methicillin resistance ; Membrane ; Cell membrane leakage ; Structure&ndash ; activity relationship
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：26
• 期：9
• 页码：2324-2327
• 全文大小：652 K

文摘

Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of these compounds, we synthesized acyclic fragment structures and evaluated their anti-MRSA activity. The activities of all of the acyclic fragments tested exhibited similar characteristics to those of the macrocycles, i.e., anti-MRSA bactericidal activity, an enhancing effect on influx and efflux of ethidium bromide (EtBr: fluorescent DNA-binder) in Staphylococcus aureus cells, and bactericidal activity towards a Staphylococcus aureus strain resistant to 2-phenoxyphenol (4). The latter result suggests that they have a different mechanism of action from 4, which is a FabI inhibitor previously proposed to be the minimum active fragment of riccardin-type macrocycles. Thus, cyclic structure is not a necessary condition for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s.