Design,synthesis, and biological evaluation of new arylamide derivatives possessing sulfonate or sulfamate moieties as steroid sulfatase enzyme inhibitors |
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| Institution: | 1. Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;2. Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates;3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt;4. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom;5. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2HT, United Kingdom;6. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom |
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| Abstract: | A series of new arylamide derivatives possessing terminal sulfonate or sulfamate moieties was designed and synthesized. The target compounds were tested for in vitro inhibitory effects against the steroid sulfatase (STS) enzyme in a cell-free assay system. The free sulfamate derivative 1j was the most active. It inhibited the enzymatic activity by 72.0% and 55.7% at 20 μM and 10 μM, respectively. Compound 1j was further tested for STS inhibition in JEG-3 placental carcinoma cells with high STS enzyme activity. It inhibited 93.9% of the enzyme activity in JEG-3 placental carcinoma cells at 20 μM with an efficacy near to that of the well-established drug STX64 as reference. At 10 μM, 1j inhibited 86.1% of the STS activity of JEG-3. Its IC50 value against the STS enzyme in JEG-3 cells was 0.421 μM. Thus, 1j represents an attractive new non-steroidal lead for further optimization. |
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| Keywords: | Arylamide JEG-3 Steroid sulfatase Sulfamate Sulfonate |
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