Ascochlorin derivatives as ligands for nuclear hormone receptors

Marie Togashi, Satoshi Ozawa, Shoko Abe, Tomoyuki Nishimura, Mie Tsuruga, Kunio Ando, Gakuzo Tamura, Shigefumi Kuwahara, Makoto Ubukata, Junji Magae

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor γ (PPARγ). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylascochlorin (10), showed improved agonistic activity for PPARγ and induced differentiation of a progenitor cell line, C3H10T1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-O-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARα, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.

Original languageEnglish
Pages (from-to)4113-4123
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number19
Publication statusPublished - 2003 Sep 11

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


Dive into the research topics of 'Ascochlorin derivatives as ligands for nuclear hormone receptors'. Together they form a unique fingerprint.

Cite this