targeted anticancer drug discovery from borassus flabellifer fruit peel extract: a molecular mechanism study

Cancer remains one of the leading causes of mortality worldwide. conventional treatments, such as chemotherapy and radiotherapy, are often limited by severe side effects and low selectivity toward healthy cells. consequently, natural metabolites explored through in silico approaches offer promising opportunities to discover safer anticancer agents. metabolite profiling of the ethanolic extract of palmyra (borassus flabellifer) fruit peel identified 80 metabolites, with 55 compounds showing a match score of ≥80%. these 55 compounds were further analyzed in silico for their potential biological activity. network pharmacology analysis predicted molecular targets associated with breast cancer, revealing p53 as the central hub with the highest degree value, followed by akt1 and egfr as key nodes. candidate metabolites were then evaluated against mutant p53 (pdb id: 2vuk) using molecular docking, followed by 100 ns molecular dynamics (md) simulations and mm-gbsa binding free energy analysis to validate the stability and affinity of ligand–protein interactions. docking results indicated that 7-methoxy-3′,4′-dihydroxyflavonone (–6.95 kcal/mol) displayed affinities comparable to the reference stabilizing ligand (–7.18 kcal/mol). md simulations confirmed stable interactions with key residues surrounding the y220c mutation pocket, supported by consistent rmsd and rmsf profiles throughout the 100 ns trajectory. furthermore, mm-gbsa analysis highlighted 7-methoxy-3′,4′-dihydroxyflavonone (–52.11 kcal/mol) as exhibiting stronger binding free energy than both the reference ligand (–51.40 kcal/mol). overall, the integration of metabolite profiling, network pharmacology, molecular docking, md, and mm-gbsa analyses suggests that 7-methoxy-3′,4′-dihydroxyflavonone from palmyra fruit peel represents a potential stabilizer of mutant p53 (y220c), offering a promising strategy for targeted anticancer therapy. these findings warrant further in vitro and in vivo validation.