Molecular design, chemical synthesis, and biological evaluation of agents that selectively photo-degrade the transcription factor estrogen receptor-α

Kana Tsumura, Akane Suzuki, Takeo Tsuzuki, Shuho Tanimoto, Hajime Kaneko, Shuichi Matsumura, Masaya Imoto, Kazuo Umezawa, Daisuke Takahashi, Kazunobu Toshima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

2-Phenylquinoline (1) degraded proteins under photo-irradiation with long-wavelength UV light without additives and under neutral conditions. We designed and synthesized a 2-phenylquinoline-estrogen receptor-α (ER-α) agonist (hybrid 2) and a 2-phenylquinoline-ER-α antagonist (hybrid 3) containing estradiol and 4-hydroxytamoxifen moieties, respectively. These 2-phenylquinoline hybrids effectively and selectively photo-degraded the target transcription factor, ER-α, which has a high affinity for estradiol and 4-hydroxytamoxifen. Target-selective photo-degradation was examined in both glass vessels and MCF-7 breast cancer cells, which are dependent upon ER-α for growth. In addition, 2-phenylquinoline-estradiol hybrid 2 functioned as an agonist of ER-α and promoted growth of MCF-7 in the absence of photo-irradiation, while it inhibited the growth of MCF-7 cells upon photo-irradiation due to the photo-degradation of ER-α. In contrast, 2-phenylquinoline-4-hydroxytamoxifen hybrid 3 inhibited growth of MCF-7 cells in the absence of photo-irradiation due to the antagonist effect of the 4-hydroxytamoxifen moiety against ER-α, and upon photo-irradiation significantly inhibited cell growth due to the dual antagonist effect of the 4-hydroxytamoxifen moiety and photo-degradation of ER-α.

Original languageEnglish
Pages (from-to)6357-6366
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume9
Issue number18
DOIs
Publication statusPublished - 2011 Sep 21

Fingerprint

estrogens
Biological Factors
Estrogen Receptors
Transcription Factors
Irradiation
evaluation
Photodegradation
synthesis
Growth
Estradiol
irradiation
MCF-7 Cells
Estrogens
degradation
Cell growth
Ultraviolet Rays
Ultraviolet radiation
Glass
2-phenylquinoline
cells

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Molecular design, chemical synthesis, and biological evaluation of agents that selectively photo-degrade the transcription factor estrogen receptor-α. / Tsumura, Kana; Suzuki, Akane; Tsuzuki, Takeo; Tanimoto, Shuho; Kaneko, Hajime; Matsumura, Shuichi; Imoto, Masaya; Umezawa, Kazuo; Takahashi, Daisuke; Toshima, Kazunobu.

In: Organic and Biomolecular Chemistry, Vol. 9, No. 18, 21.09.2011, p. 6357-6366.

Research output: Contribution to journalArticle

Tsumura, Kana ; Suzuki, Akane ; Tsuzuki, Takeo ; Tanimoto, Shuho ; Kaneko, Hajime ; Matsumura, Shuichi ; Imoto, Masaya ; Umezawa, Kazuo ; Takahashi, Daisuke ; Toshima, Kazunobu. / Molecular design, chemical synthesis, and biological evaluation of agents that selectively photo-degrade the transcription factor estrogen receptor-α. In: Organic and Biomolecular Chemistry. 2011 ; Vol. 9, No. 18. pp. 6357-6366.
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