2. Academic Validation
  3. Synthesis of bicoumarin thiophosphate derivatives as steroid sulfatase inhibitors

Synthesis of bicoumarin thiophosphate derivatives as steroid sulfatase inhibitors

  • Eur J Med Chem. 2015 Aug 28:101:358-66. doi: 10.1016/j.ejmech.2015.06.051.
Sebastian Demkowicz 1,  Witold Kozak 2,  Mateusz Daśko 2,  Maciej Masłyk 3,  Bartłomiej Gielniewski 3,  Janusz Rachon 2
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland. Electronic address: [email protected].
  • 2 Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland.
  • 3 Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708 Lublin, Poland.
PMID: 26163883 DOI: 10.1016/j.ejmech.2015.06.051
Abstract

Based on the frameworks of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one, a series of bicoumarin thiophosphate analogs have been synthesized and biologically evaluated. Additionally, their binding modes have been modeled using docking techniques. The inhibitory properties of the synthesized compounds were tested against the STS isolated from human placenta. Most of the new STS inhibitors possessed good activities against STS. In particular, we found that the bis-(6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl) hydrogenthiophosphate (10b) produced the largest inhibitory effect, with an IC50 value of 860 nM (an IC50 value of 1 μM for the 665-COUMATE used as a reference). The structure-activity relationships of the synthesized bicoumarin thiophosphate derivatives toward the STS enzyme have been discussed previously.

Keywords

Bicoumarin thiophosphates; Breast cancer; Molecular docking; STS inhibitors; Steroid sulfatase.

Figures