Design and synthesis of 3-benzylaminocoumarin-7-O-sulfamate derivatives as steroid sulfatase inhibitors
| Autor: | I-Chen Liu, I-Chun Lin, Pei-Fang Chiu, Keng-Chang Tsai, Tzung-Sheng Lin, Yeh-Lin Lu, Chiao-Nien Chang, Yue Hng, Mei-Hsiang Lin, Pi-Hui Liang, Mei-Jou Chen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
Placenta 01 natural sciences Biochemistry Steroid chemistry.chemical_compound Structure-Activity Relationship Sulfation Coumarins Pregnancy Drug Discovery Benzyl Compounds medicine Steroid sulfatase Humans Enzyme Inhibitors Molecular Biology IC50 Amination chemistry.chemical_classification 010405 organic chemistry Sulfatase Organic Chemistry Coumarin 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme chemistry Cell culture MCF-7 Cells Female Steryl-Sulfatase Sulfonic Acids |
| Zdroj: | Bioorganic chemistry. 96 |
| ISSN: | 1090-2120 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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