Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents

Kohei Torikai, Rintaro Koga, Xiaohui Liu, Kaoru Umehara, Tatsuya Kitano, Kenji Watanabe, Tohru Oishi, Hiroshi Noguchi, Yasuyuki Shimohigashi

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 < μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs).

元の言語英語
ページ(範囲)5216-5237
ページ数22
ジャーナルBioorganic and Medicinal Chemistry
25
発行部数20
DOI
出版物ステータス出版済み - 1 1 2017

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Estrogens
Estrogen Receptors
Orphan Nuclear Receptors
Selective Estrogen Receptor Modulators
Inhibitory Concentration 50
Osteoporosis
Libraries
Breast Neoplasms
Derivatives

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

Torikai, K., Koga, R., Liu, X., Umehara, K., Kitano, T., Watanabe, K., ... Shimohigashi, Y. (2017). Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents. Bioorganic and Medicinal Chemistry, 25(20), 5216-5237. https://doi.org/10.1016/j.bmc.2017.07.067

Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents. / Torikai, Kohei; Koga, Rintaro; Liu, Xiaohui; Umehara, Kaoru; Kitano, Tatsuya; Watanabe, Kenji; Oishi, Tohru; Noguchi, Hiroshi; Shimohigashi, Yasuyuki.

:: Bioorganic and Medicinal Chemistry, 巻 25, 番号 20, 01.01.2017, p. 5216-5237.

研究成果: ジャーナルへの寄稿記事

Torikai, K, Koga, R, Liu, X, Umehara, K, Kitano, T, Watanabe, K, Oishi, T, Noguchi, H & Shimohigashi, Y 2017, 'Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents', Bioorganic and Medicinal Chemistry, 巻. 25, 番号 20, pp. 5216-5237. https://doi.org/10.1016/j.bmc.2017.07.067
Torikai, Kohei ; Koga, Rintaro ; Liu, Xiaohui ; Umehara, Kaoru ; Kitano, Tatsuya ; Watanabe, Kenji ; Oishi, Tohru ; Noguchi, Hiroshi ; Shimohigashi, Yasuyuki. / Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents. :: Bioorganic and Medicinal Chemistry. 2017 ; 巻 25, 番号 20. pp. 5216-5237.
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