The potential of 5-O-acylpinostrobin derivatives against progesterone and EGFR-HER2 receptors as anti-breast cancer: Docking, molecular dynamics simulations, and ADMET prediction

Context: Breast cancer involves uncontrolled proliferation of breast tissue and remains the leading cause of cancer-related mortality in women. Progesterone receptors modulate estrogen-α receptor signaling, while EGFR-HER2 overexpression promotes cancer cell proliferation and therapy resistance. Pinostrobin, isolated from Boesenbergia pandurata, exhibits anticancer activity, and its structural modification to 5-O-acylpinostrobin derivatives may enhance potency. Aims: To predict the potential of 5-O-acylpinostrobin derivatives against progesterone and EGFR-HER2 receptors through molecular docking, molecular dynamics simulations, and ADMET predictions. Methods: Molecular docking was performed using MOE 2022.02, followed by 100 ns molecular dynamics simulations with AMBER 20, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were evaluated using ADMETlab. Results: All derivatives showed stronger binding affinities than pinostrobin, with pinostrobin butyrate demonstrating the highest stability during molecular dynamics to both receptors. ADMET predictions indicated favorable pharmacokinetics, although with potential carcinogenicity. Conclusions: These findings indicate that pinostrobin butyrate exhibits promising candidate for further preclinical development as an anti-breast cancer agent.