Phytochemical Composition and Biological Activities of Unripe Ricinus communis Fruits with Protein–Ligand Docking Interaction Study

Abstract

Plant-derived metabolites have attracted considerable attention with increasing interest in sustainable, bio-based resources for biological applications. HPLC analysis of unripe Ricinus communis fruits revealed a rich profile of phenolic compounds, with hesperetin (42400 µg/g) and chlorogenic acid (14300 µg/g). The extract exhibited antimicrobial activity. It produced inhibition zones of 23 to 31 mm for examined bacteria and 32 mm against Candida albicans, with minimum inhibitory concentrations as low as 15.6 µg/mL. Biofilm formation was inhibited by up to 97.8%. Cytotoxic evaluation showed anticancer activity against a human epidermoid carcinoma cell line (A431), with an IC₅₀ of 76.8 µg/mL compared to 359 µg/mL for normal HFB4 cells. Antibacterial and anticancer potential of hesperetin (main constituent of unripe R. communis fruits) through molecular docking against PBP2a from S. aureus (PDB ID: 4CJN) and EGFR kinase domain (PDB ID: 2GS6) were reported. Hesperetin exhibited favorable binding toward both targets, with docking scores ranging from -5.12 to -5.47 kcal/mol for PBP2a and -5.98 to -6.53 kcal/mol for EGFR. Key hydrogen bonding interactions were observed with GLN521 in PBP2a and ASP831 in EGFR, indicating stable ligand-protein complexes. Notably, hesperetin demonstrated stronger binding affinity toward EGFR, suggesting enhanced anticancer potential. Docking-supported hesperetin-rich extract exhibited antimicrobial resistance inhibition and selective anticancer activity.