Background:
Some reports have demonstrated the role of the G Protein-coupled Estrogen
Receptor (GPER) in growth and proliferation of breast cancer cells.
Objective:
In an effort to develop new therapeutic strategies against breast cancer, we employed an in
silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported
ligands G1 and G1PABA.
Methods:
This study aimed to design and filter ligands by in silico studies determining their Lipinski's
rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative
compounds of breast cancer cell lines.
Results:
In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl
group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high
hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and
molecular dynamics simulations of the target compounds were performed with GPER to explore their
binding mode and free energy values. In addition, the target small molecules were synthesized and assayed
in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that
compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment
of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar
inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands
reach the GPER-binding site in a similar way, as was demonstrated through in silico studies.
Conclusion:
A concentration-dependent inhibition of cell proliferation occurred with compound 2 in
the two cell lines regardless of GPER.
A Study on the Preparation and Characterization of Curcumin and Gold Nanorods-loaded Albumin Nanoparticles and its Treatment of MCF-7 Breast Cancer Cells in Vitro
