Antioxidant potential of a new macrocyclic bisbibenzyl and other compounds from Combretum molle: in vitro and docking analyses

Introduction: Free radicals are key contributors to several diseases, including cancer, inflammation, pain, andneurodegenerative disorders such as Alzheimer’s disease. Due to the limitations and adverse effects of syntheticantioxidants, naturally occurring phytochemicals offer safer, more sustainable alternatives. This study investigatesthe antioxidant potential of twigs of Combretum molle R. Br. ex G. Don through integrated experimentaland computational approaches.Methods: Compounds were isolated using chromatographic methods, and their structures established by 1Dand2D-NMR, HR-ESI-MS, and comparison with reported data. Antioxidant activity was assessed through DPPHradical scavenging and FRAP assays, while molecular docking against xanthine oxidase (PDB: 1FIQ) explored possible mechanisms beyond direct radical scavenging.Results: A new macrocyclic bisbibenzyl derivative, combrebisbibenzyl A (1), was identified along with corosolicacid (2), maslinic acid (3), a mixture of asiatic acid (4) and arjunolic acid (5), combregenin (6), and β-sitosterolglucoside (7). The MeOH extract and EtOAc fraction showed notable DPPH scavenging activity (IC₅₀ = 170.21 and197.41 μg/mL) and strong reducing power (65.04 ± 1.07 and 67.42 ± 0.82 mM Vit C/g). Among the isolated compounds, combrebisbibenzyl A (1) displayed the strongest radical scavenging effect (IC₅₀ = 175.64 μg/mL) and high reducing capacity (57.46 ± 0.42 mM Vit C/g). Docking indicated favorable interactions for all compounds, withcombrebisbibenzyl A (1) showing the highest affinity (–9.1 kcal/mol), outperforming salicylate (–7.7 kcal/mol).Conclusion: These findings support the traditional use of C. molle and highlight combrebisbibenzyl A (1) as apromising natural antioxidant with multi-mechanistic potential.