Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 15, Issue 11, Pages 1035-1042Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568026615666150317221549
Keywords
Breast cancer; Carbazole derivatives; Docking simulations; Estrogen/estrogen receptors; GPR30/GPER; Heterocycles
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [12849/2012]
- AIRC project Calabria
- Fondazione Cassa di Risparmio di Calabria e Lucania [PON01_01078]
- Ministero della Salute Grant [67/GR-2010-2319511]
- Compagnia di San Paolo di Torino
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Estrogens control a wide number of aspects of human physiology and play a key role in multiple diseases, including cancer. Estrogens act by binding to and activating the cognate receptor (ER), however numerous studies have revealed that the G protein-coupled receptor named GPR30/GPER mediates also estrogen signals. As ER and GPER share the ability to bind to same compounds, the use of GPER-selective ligands has allowed a better understanding of the biological responses mediated by GPER. In the present study, we designed and synthesized two novel carbazole derivatives and then investigated their ability to interact with and activate the GPER-mediated transduction pathway in breast cancer cells. Both compounds did not activate the classical ER in MCF7 cells, whereas one of the two compounds synthesized triggered through GPER the rapid ERK activation in ER-negative SkBr3 cells, demonstrating a good affinity for GPER in docking studies. The characterization of this novel selective GPER agonist could represent a potential useful tool to provide further insights into the physiopathological role exerted by GPER.
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