https://scholars.lib.ntu.edu.tw/handle/123456789/540229
標題: | Design and synthesis of 3-benzylaminocoumarin-7-O-sulfamate derivatives as steroid sulfatase inhibitors | 作者: | Hng, Yue Lin, Mei-Hsiang Lin, Tzung-Sheng Liu, I-Chen Lin, I-Chun Lu, Yeh-Lin Chang, Chiao-Nien Chiu, Pei-Fang Tsai, Keng-Chang MEI-JOU CHEN PI-HUI LIANG |
關鍵字: | Breast cancer; Coumarin; Hormone dependent cancer; Irreversible inhibitors; Steroid sulfatase; Sulfamate | 公開日期: | 2020 | 出版社: | ACADEMIC PRESS INC ELSEVIER SCIENCE | 卷: | 96 | 來源出版物: | Bioorganic chemistry | 摘要: | Steroid sulfatase (STS) is a sulfatase enzyme that catalyzes the conversion of sulfated steroid precursors to free steroid. The inhibition of STS could abate estrogenic steroids that stimulate the proliferation and development of breast cancer, and therefore STS is a potential target for adjuvant endocrine therapy. In this study, a series of 3-benzylaminocoumarin-7-O-sulfamate derivatives targeting STS were designed and synthesized. Structure-relationship activities (SAR) analysis revealed that attachment of a benzylamino group at the 3-position of coumarin improved inhibitory activity. Compound 3j was found to have the highest inhibition activity against human placenta isolated STS (IC50 0.13 μM) and MCF-7 cell lines (IC50 1.35 µM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with KI and kinact value of 86.9 nM and 158.7 min-1, respectively. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/540229 | ISSN: | 0045-2068 | DOI: | 10.1016/j.bioorg.2020.103618 | SDG/關鍵字: | 3 (2,3 dimethoxybenzyl)aminocoumarin 7 o sulfamate; 3 benzylaminocoumarin 7 o sulfamate derivative; benzamide derivative; coumarin derivative; enzyme inhibitor; growth hormone; irosustat; steryl sulfatase; unclassified drug; benzyl derivative; coumarin derivative; enzyme inhibitor; steryl sulfatase; STS protein, human; sulfamic acid; sulfonic acid derivative; Article; breast cancer; drug design; drug structure; drug synthesis; enzyme inhibition; human; human cell; MCF-7 cell line; placenta; priority journal; structure activity relation; amination; chemistry; enzymology; female; metabolism; pregnancy; synthesis; Amination; Benzyl Compounds; Coumarins; Enzyme Inhibitors; Female; Humans; MCF-7 Cells; Placenta; Pregnancy; Steryl-Sulfatase; Structure-Activity Relationship; Sulfonic Acids |
顯示於: | 藥學系 |
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