Integrative Approach of Virtual Screening, Synthesis, and Cytotoxicity Evaluation Towards Inhibition of Breast Cancer Targeting G Protein-coupled Estrogen Receptor 1 (GPER1)

G protein-coupled estrogen receptor-1 (GPER1) has been proposed as a new therapeutic target in triple-negative breast cancer and tamoxifen resistance cancer. Due to the lack of the crystal structure of GPER1, sequential ligand-based and structure-based screening approaches were used to identify new potential GPER1 modulators. For prospective validation, a new, efficient, simple, and one-pot synthesis was developed to synthesise fifty (50) different compounds. Evaluation of their biological activity revealed some new compounds possessing specific anticancer activity. Five top hits compounds, SK0, SK0P, SK-29, SK-37 and SK-39 were identified as a new GPER1 modulators that need further investigations in breast cancer treatment.