Computational evaluation of soy-derived isoflavones, polyamines, and anthocyanins as multi-target modulators in anti-aging pathways

Fermented soy foods provide bioactive isoflavones, anthocyanins, and polyamines that may influence aging-related mechanisms. To justify target and compound prioritization, we first conducted a bibliometric mapping of the recent literature linking fermented soy bioactives to aging pathways, which supported focusing on mTOR (nutrient sensing/autophagy), iNOS (inflammaging), and ROS1 (kinase/redox-relevant signaling) as structurally tractable targets with available co-crystal data. Isoflavones (genistein, daidzein, glycitein, equol), anthocyanins (delphinidin, cyanidin, pelargonidin), and polyamines (spermidine, spermine, putrescine) were curated from PubChem based on reported occurrence in fermented soy matrices and profiled using SwissADME. Consensus molecular docking was performed against human mTOR (3FAP), iNOS (3E7G), and ROS1 (3ZBF), with protocol validation by redocking co-crystallized ligands (RMSD < 2 Å). Equol showed the strongest predicted binding to mTOR (ΔG ≈ −6.36 kcal/mol; Ki ≈ 21.8 μM), genistein to iNOS (ΔG ≈ −9.93 kcal/mol; Ki ≈ 0.052 μM), and delphinidin to ROS1 (ΔG ≈ −7.91 kcal/mol; Ki ≈ 1.59 μM). Molecular dynamics simulations (100 ns) provided supportive evidence of stable binding modes for the top-ranked complexes. These results are hypothesis-generating; physiological relevance at dietary exposure levels remains uncertain, and no mixture/synergy effects were tested, warranting experimental validation.