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

Research output: Contribution to journalArticlepeer-review

Authors

  • Mohammed El-Gamal
  • Mohammad Semreen
  • Paul Foster
  • Barry Potter

Colleges, School and Institutes

External organisations

  • Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, UAE
  • Department of Pharmacology, University of Oxford, Oxford

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.

Details

Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume24
Issue number12
Early online date22 Apr 2016
Publication statusPublished - 15 Jun 2016

Keywords

  • Arylamide , JEG-3 , Steroid sulfatase , Sulfamate , Sulfonate