Investigation of compounds as ERK5 inhibitor related to breast cancer via molecular docking and dynamic simulation.

UNLABELLED

Breast cancer remains a global health challenge, with rising cases predicted in the coming decades. The complexity of breast cancer treatment arises from its complex nature, often involving multiple therapeutic strategies. One promising approach is targeting the ERK5 pathway, a key regulator in cancer cell proliferation and survival. In this study, we explored the anticancer potential of bioactive compounds from , a plant traditionally used in West African medicine. The 3D structure of ERK5 (PDB ID: 4B99) was prepared and optimized using the Schrödinger Protein Preparation Wizard. Six phytochemicals from were screened for their binding affinities to ERK5 using GlideXP docking. Dihydrogingerenone A,1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl) heptane-3,5-diyldiacetate and Dihydrogingerenone C emerged as the lead compound, demonstrating a high docking score of -  9.659 kcal/mol, -  9.383 kcal/mol, and - 8.264 kcal/mol compared to standard anticancer drugs like Docetaxel (- 4.175 kcal/mol) and Temozolomide (- 5.443 kcal/mol). Post-docking analyses using MM-GBSA free energy calculations confirmed the compound's high binding stability, with van der Waals interactions and hydrogen bonding at critical residues such as Met140 playing a significant role. Pharmacokinetic profiling using ADME analysis showed that our compounds exhibited favorable drug-likeness properties, adhering to Lipinski's Rule of Five without violations. QSAR modeling and molecular dynamics (MD) simulations further validated its pharmacological potential. These findings suggest that contains bioactive compounds with strong potential as ERK5 inhibitors, offering a novel approach to breast cancer treatment.

GRAPHICAL ABSTRACT

The molecular docking study of Dihydrogingerenone A, 1-(3, 4-dihydroxy-5-methoxyphenyl)-7-(3, 4-dihydroxyphenyl) heptane-3, 5-diyldiacetate, and Dihydrogingerenone C from as effective breast cancer treatment.