Harnessing Annona muricata phytochemicals for multi-target cancer therapy: An integrated network pharmacology and in-silico study

Lung and breast cancers are among the major causes of cancer-related morbidity and mortality worldwide. Both these cancers share several dysregulated molecular processes, including common oncogenic signaling pathways and molecular targets. Therefore, the current study focuses on the dual anticancer potential of Annona muricata. Natural products from medicinal plants are recognized as valuable sources of bioactive compounds with potential anticancer activity. In the present study, an integrated network pharmacology and in-silico approach was employed to identify potential phytoconstituents from Annona muricata against lung and breast cancers. Initially, 63 phytochemicals were collected from the IMPPAT database and screened using ADMET and toxicity prediction, resulting in nine compounds with favorable pharmacokinetic and safety profiles. Network pharmacology identified 12,321 common genes associated with both cancers, from which 209 potential targets were obtained. Protein-protein interaction analysis identified key hub genes, including HSP90AA1, MMP9, HIF1A, and MDM2, for molecular docking. Docking revealed that HIF-1α (PDB ID: 3KCX) provided the most favorable binding environment. Among the screened phytochemicals, (-)-Coreximine showed the strongest interaction with HIS199 and ASP201. MM-GBSA confirmed its highest binding affinity (-39.47 kcal/mol), while DFT and molecular dynamics simulations demonstrated stability and persistent binding. Overall, these computational findings suggest that (-)-Coreximine may attenuate cancer progression through modulation of HIF-1α-associated pathways and represents a promising natural lead for further investigation.