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

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

  • Bioorg Med Chem. 2016 Jun 15;24(12):2762-7. doi: 10.1016/j.bmc.2016.04.040.
Mohammed I El-Gamal 1,  Mohammad H Semreen 2,  Paul A Foster 3,  Barry V L Potter 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt. Electronic address: drmelgamal2002@gmail.com.
  • 2 Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 3 Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2HT, United Kingdom. Electronic address: P.A.Foster@bham.ac.uk.
  • 4 Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom.
PMID: 27143133 DOI: 10.1016/j.bmc.2016.04.040
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 20μM and 10μM, 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 20μM with an efficacy near to that of the well-established drug STX64 as reference. At 10μM, 1j inhibited 86.1% of the STS activity of JEG-3. Its IC50 value against the STS Enzyme in JEG-3 cells was 0.421μM. Thus, 1j represents an attractive new non-steroidal lead for further optimization.

Keywords

Arylamide; JEG-3; Steroid sulfatase; Sulfamate; Sulfonate.

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