Towards β-selectivity in functional estrogen receptor antagonists - Publication - Bridge of Knowledge

Search

Towards β-selectivity in functional estrogen receptor antagonists

Abstract

Based on the benzo[b]naphtho[1,2-d]furan and benzo[b]naphtho[1,2-d]thiophene frameworks, a series of ligands with different basic side chains (BSCs) has been synthesized and pharmacologically evaluated. Also, their binding modes have been modelled using docking techniques. It was found that the introduction of a BSC in these systems brings about a decrease of affinity for both estrogen receptors α and β in an in vitro competitive binding assay. However, two full antagonists of the estrogen receptor β (9c and 9f) have been discovered, with potency in the low micromolar concentration in a cell-based luciferase reporter assay, and completely devoid of activity against the α receptor at the same concentration range. Differences in the ERα/ERβ binding modes have also been rationalized with the help of molecular modelling techniques. This interesting functional profile could be used to elucidate the physiological role of each ER subtype.

Citations

  • 7

    CrossRef

  • 0

    Web of Science

  • 8

    Scopus

Authors (9)

  • Photo of  Jose Juan Rodríguez

    Jose Juan Rodríguez

    • Universidad CEU San Pablo Departamento de Química, Facultad de Farmacia
  • Photo of  Kamila Filipiak

    Kamila Filipiak

    • The John Paul II Catholic University of Lublin, Department of Molecular Biology, Faculty of Mathematics and Natural Sciences
  • Photo of  Maciej Maslyk

    Maciej Maslyk

    • The John Paul II Catholic University of Lublin, Department of Molecular Biology, Faculty of Mathematics and Natural Sciences
  • Photo of  Jakub Ciepielski

    Jakub Ciepielski

    • The John Paul II Catholic University of Lublin, Department of Environmental Biochemistry and Chemistry, Faculty of Mathematics and Natural Sciences
  • Photo of  Sonia de Pascual-Teresa

    Sonia de Pascual-Teresa

    • Spanish National Research Council (CSIC) Institute of Food Science, Food Technology and Nutrition (ICTAN)
  • Photo of  Sonsoles Martín-Santamaría

    Sonsoles Martín-Santamaría

    • Universidad CEU San Pablo Departamento de Química, Facultad de Farmacia
  • Photo of  Beatriz de Pascual-Teresa ..

    Beatriz de Pascual-Teresa ..

    • Universidad CEU San Pablo Departamento de Química, Facultad de Farmacia
  • Photo of  Ana Ramos

    Ana Ramos

    • Universidad CEU San Pablo Departamento de Química, Facultad de Farmacia

Cite as

Full text

full text is not available in portal

Keywords

Details

Category:
Articles
Type:
artykuł w czasopiśmie wyróżnionym w JCR
Published in:
ORGANIC & BIOMOLECULAR CHEMISTRY no. 10, edition 36, pages 7334 - 7346,
ISSN: 1477-0520
Language:
English
Publication year:
2012
Bibliographic description:
Rodríguez J., Filipiak K., Maslyk M., Ciepielski J., Demkowicz S., De Pascual-Teresa S., Martín-Santamaría S., .. ., Ramos A.: Towards β-selectivity in functional estrogen receptor antagonists// ORGANIC & BIOMOLECULAR CHEMISTRY. -Vol. 10, iss. 36 (2012), s.7334-7346
DOI:
Digital Object Identifier (open in new tab) 10.1039/c2ob26062j
Verified by:
Gdańsk University of Technology

seen 62 times

Recommended for you

Meta Tags