Document Type
Article
Rights
Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence
Disciplines
Biochemistry and molecular biology, Immunology
Abstract
4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).
DOI
https://doi.org/10.1016/j.bmc.2019.115261
Recommended Citation
Miriam Carr, Andrew J.S. Knox, Daniel K. Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas McCabe, Brendan Twamley, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan, Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening, Bioorganic & Medicinal Chemistry, Volume 28, Issue 5, 2020, 115261, ISSN 0968-0896, https://doi.org/10.1016/j.bmc.2019.115261.
Funder
Trinity College IITAC research initiative (HEA PRTLI); Enterprise Ireland (EI); Science Foundation Ireland (SFI); Wellcome Trust.
Included in
Biochemistry Commons, Cancer Biology Commons, Diseases Commons, Molecular Biology Commons
Publication Details
Bioorganic & Medicinal Chemistry