Design, synthesis, and biological evaluation of new arylamide derivatives possessing sulfonate or sulfamate moieties as steroid sulfatase enzyme inhibitors

Journal article

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.

Authors: El-Gamal, MI; Semreen, MH; Foster, PA; Potter, BVL

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Bioorganic and Medicinal Chemistry
• Volume: 24
• Issue: 12
• Pages: 2762-2767
• Publication date: 2016-04-22
• Acceptance date: 2016-04-21
• DOI: 10.1016/j.bmc.2016.04.040
• EISSN: 1464-3391
• ISSN: 0968-0896
• Language: English
• Keywords: arylamide; sulfonate; JEG-3; sulfamate; steroid sulfatase