Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureusopen access
- Mizar, Pushpak; Arya, Rekha; Kim, Truc; Cha, Soyoung; Ryu, Kyoung-Seok; Yeo, Won-sik; Bae, Taeok; Kim, Wook; Park, Ki Hun; Kim, Kyeong Kyu; Lee, Seung Seo
- Issue Date
- AMER CHEMICAL SOC
- JOURNAL OF MEDICINAL CHEMISTRY, v.61, no.23, pp.10473 - 10487
- Journal Title
- JOURNAL OF MEDICINAL CHEMISTRY
- Start Page
- End Page
- As an alternative strategy to fight antibiotic resistance, two-component systems (TCSs) have emerged as novel targets. Among TCSs, master virulence regulators that control the expression of multiple virulence factors are considered as excellent antivirulence targets. In Staphylococcus aureus, virulence factor expression is tightly regulated by a few master regulators, including the SaeRS TCS. In this study, we used a SaeRS GFP-reporter system to screen natural compound inhibitors of SaeRS, and identified xanthoangelol B 1, a prenylated chalcone from Angelica keiskei as a hit. We have synthesized 1 and its derivative PM-56 and shown that 1 and PM-56 both had excellent inhibitory potency against the SaeRS TCS, as demonstrated by various in vitro and in vivo experiments. As a mode of action, 1 and PM-56 were shown to bind directly to SaeS and inhibit its histidine kinase activity, which suggests a possibility of a broad spectrum inhibitor of histidine kinases.
- Files in This Item
- There are no files associated with this item.
- Appears in
- ETC > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.