In Silico Analysis of Graviola(Annona muricata) Acetogenins as Modulators of Kidney Cancer Pathways

In silico multi-target evaluation of four Annona muricata acetogenins (muricatacin, annonacin, bullatacin, and cis-uvariamicin IV) against key renal cell carcinoma-associated proteins (PI3Kα, mTOR, AKT1, Bcl-2, caspase-3) using molecular docking, ADME prediction, and toxicity profiling. A weighted composite scoring framework integrating safety, drug-likeness, mechanistic differentiation, and binding affinity was developed to identify the most translationally viable natural product scaffold. Muricatacin ranked highest across 10,000 Monte Carlo weight simulations. An exploratory scaffold modification incorporating MK-2206 structural elements demonstrated improved AKT1 engagement. All data, figures, and R code are publicly available for full reproducibility.