Annurca Apple Extract and Colorectal Cancer Prevention: Preliminary In Silico Evaluation of Chlorogenic Acid

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant and anti-inflammatory effects. This study evaluated, via molecular docking, the multi-target interaction profile of chlorogenic acid against key CRC-related proteins.

The optimized 3D structure of chlorogenic acid was docked to ten protein targets implicated in CRC pathogenesis, using the GOLD v.2022.3.0 software. Validation of the docking protocol was achieved by re-docking native ligands (RMSD ≤ 2.0 Å). Binding affinities were assessed by ChemPLP scoring, and interaction networks were visualized in Maestro Schrödinger.

Chlorogenic acid displayed consistent binding across all evaluated targets (ChemPLP 57.12-69.66), showing the highest affinity for nAChR (69.66), CXCR2 (65.13), ERβ (63.18) and TGFBR2 (62.94). The ligand formed multiple hydrogen bonds and π-π stacking interactions involving Asp1040 (VEGFR-1), Cys919 (VEGFR-2), Lys320 (CXCR2), and Tyr195 residues (nAChR), contributing to strong complex stabilization. Interaction patterns in CYP19A1, ERβ, and ERRγ suggested potential modulation of hormonal and metabolic signaling. The compound also demonstrated stable binding to mTOR (60.01), indicating a possible inhibitory role in proliferative pathways. Collectively, these findings reveal a broad, polypharmacological binding profile involving angiogenic, inflammatory, and hormonal regulators.

Chlorogenic acid acts as a promising multi-target ligand in CRC prevention, with our in silico evidence supporting its ability to modulate diverse oncogenic pathways. Further experimental studies are warranted to confirm its efficacy and translational potential.