Indole‐2‐carboxamide derivatives as G‐protein coupled Estrogen (GPER/GPR30) ligands

Classical estrogen receptors (estrogen receptors α and β), have been shown to cause cell proliferation in a variety of breast cancers upon interaction with estrogenic compounds; however, G‐protein estrogen receptor (GPER) has also been linked to cell proliferation, when in the presence of estrogens in breast cancers absent Estrogen receptors α and β. Here we demonstrate the ability of small molecules, specifically computationally modeled hits that may interact with GPER, to inhibit estrogen binding to GPER. Interactions of these modeled hits were studied on breast cancer cell lines SKBR3, MCF7, and MDA‐MB‐231's in an estrogen promoted antiproliferation assays to search for potential activity with the GPER to determine estrogenic interactions upon the breast cancer lines. These interactions may signify that inhibition of GPER to block estrogen is an effective method for curbing estrogen promoted cancer cell proliferation. Specifically, within MBA‐MD‐231 cells, compounds showed inhibition of growth similar to the GPER selective agonist G‐1, which is consistent with previously published results.