Design, Structure–Activity Relationships, and Enzyme Kinetic Studies of Tricyclic and Tetracyclic Coumarin–based Sulfamates as Steroid Sulfatase Inhibitors

Pei-Fang Chiu, I-Chun Lin, Yeh-Lin Lu, Chiao-Nien Chang, Hui-Yu Chan, Tzung-Shen Lin, Keng-Chang Tsai, Yves S. Y. Hsieh, Mei-Jou Chen, Mei-Hsiang Lin, Pi-Hui Liang

研究成果: 雜誌貢獻文章同行評審

摘要

Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with KI of 0.05 and 0.4 nM, and kinact/KI ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively.
原文英語
文章編號106581
期刊Bioorganic Chemistry
138
DOIs
出版狀態已發佈 - 9月 2023

ASJC Scopus subject areas

  • 藥物發現
  • 分子生物學
  • 生物化學
  • 有機化學

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