Synthesis and in vitro evaluation of novel liver X receptor agonists based on naphthoquinone derivatives

Tatsuma Nishioka, Kaori Endo-Umeda, Yuki Ito, Akane Shimoda, Atsuko Takeuchi, Chisato Tode, Yoshihisa Hirota, Naomi Osakabe, Makoto Makishima, Yoshitomo Suhara

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


We aimed to synthesize novel liver X receptor (LXR) agonists with potent agonist activity and subtype selectivity. Our synthetic scheme started with naphthoquinone derivatives, such as menadione and 2,3-dichloro-1,4-naphthoquinone. We introduced different substituents into the naphthoquinone structures, including aniline, piperidine, pyrrolidine, and morpholine, in one or two steps, and thus, we produced 14 target compounds. All 14 synthetic ligands were tested to determine whether they mediated LXR-mediated transcriptional activity. We investigated the transcriptional activity of each compound with two types of receptors, LXRα and LXRβ. Among all 14 compounds, two showed weak LXRβ-agonist activity, and two others exhibited potent LXRα-agonist activity. We also performed docking studies to obtain a better understanding of the modes of compound binding to LXR at the atomic level. In conclusion, we successfully synthesized naphthoquinone derivatives that act as LXRα/β agonists and selective LXRα agonists.

Original languageEnglish
Article number4316
Issue number23
Publication statusPublished - 2019 Nov 26


  • Agonist
  • Liver X receptor (LXR)
  • Naphthoquinone
  • Transcriptional activity
  • α-selective

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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