Virtual screening of flavonoids from Blighia sapida against ERK5 involved in breast cancer

Breast cancer is a major public health concern worldwide, with a need for effective treatments that have minimal side effects. Flavonoids have been shown to have potential as anticancer agents. In this study, the inhibitory effect of flavonoids from Blighia sapida on the breast cancer target, Extracellular signal-regulated kinase 5 (ERK5) was evaluated. A pharmacophore hypothesis was developed based on the interactions between the target protein and its co-crystallized ligand and then applied to the screening of flavonoids present in B. sapida. The top-ranked flavonoids were identified using molecular docking, MMGBSA, and pharmacokinetics modeling, and their inhibitory activity was determined using density functional theory (DFT) and their pIC50 values. The results showed that Quercetin, Kaempferol, and ( +)-Catechin had higher docking scores and obeyed the Lipinski rule of five, indicating their potential as lead molecules for ERK5 inhibition in breast cancer therapy. The study highlights the potential of flavonoids from B. sapida as promising inhibitors of ERK5 for breast cancer management.