Pinostrobin pentanoate as a selective estrogen receptor-α antagonist in breast cancer: integrated in silico and in vitro evaluation.

BACKGROUND AND PURPOSE: Breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. Estrogen receptor alpha (ERα) plays a major role in breast cancer cell proliferation, and approximately 70-80% of breast cancer cases are classified as Erα-positive. This study aims to predict the pinostrobin pentanoate potential against ERα by docking and molecular dynamics, and determine its cytotoxic activity against T47D breast cancer cells and normal cells. EXPERIMENTAL APPROACH: Docking was analyzed using MOE 2022.02. Furthermore, AMBER 20 was used for molecular dynamics. Cytotoxicity was assessed using the MTT assay against T47D breast cancer cells and Vero cells for its selectivity index (SI). FINDINGS/RESULTS: Based on docking results, the binding free energy of pinostrobin pentanoate (-7.682 ± 0.145 kcal/mol) was lower compared to pinostrobin (-6.503 ± 0.153 kcal/mol) against ERα, indicating the stronger binding affinity. In addition, the stability interaction using 100 ns molecular dynamics showed a stable interaction. Moreover, the IC50 values of pinostrobin and pinostrobin pentanoate against T47D cells were 160 ± 5.30 μM and 32 ± 3.64 μM, respectively, compared to doxorubicin 0.14 ± 0.04 μM. Meanwhile, the CC50 values of pinostrobin and pinostrobin pentanoate from the cytotoxicity test on Vero cells were estimated to be > 2500 and > 1500 μM, respectively. Therefore, the SI value of pinostrobin (SI > 15.6) is estimated to be smaller than that of pinostrobin pentanoate (SI > 46.8). Additionally, the combination of pinostrobin pentanoate and doxorubicin showed synergistic efficacy. CONCLUSION AND IMPLICATIONS: Pinostrobin pentanoate is more selective than pinostrobin, and it can be used as an anti-breast cancer candidate against the ERα for further research.