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Design and synthesis of 3-benzylaminocoumarin-7- O- sulfamate derivatives as steroid sulfatase inhibitors

Bioorganic Chemistry, ISSN: 0045-2068, Vol: 96, Page: 103618
2020
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Article Description

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 (IC 50   0.13 μM) and MCF-7 cell lines (IC 50 1.35 µM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with K I and k inact value of 86.9 nM and 158.7 min −1, respectively.

Bibliographic Details

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; Chen, Mei-Jou; Liang, Pi-Hui

Elsevier BV

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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