Hng, YueYueHngLin, Mei-HsiangMei-HsiangLinLin, Tzung-ShengTzung-ShengLinLiu, I-ChenI-ChenLiuLin, I-ChunI-ChunLinLu, Yeh-LinYeh-LinLuChang, Chiao-NienChiao-NienChangChiu, Pei-FangPei-FangChiuTsai, Keng-ChangKeng-ChangTsaiMEI-JOU CHENPI-HUI LIANG2021-01-092021-01-0920200045-2068https://scholars.lib.ntu.edu.tw/handle/123456789/540229Steroid 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.enBreast cancer; Coumarin; Hormone dependent cancer; Irreversible inhibitors; Steroid sulfatase; Sulfamate[SDGs]SDG33 (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 Acids10.1016/j.bioorg.2020.10361832059152WOS:000516796900015