Flavonoids from Algerian Propolis as Potent Antioxidants and ACE2 Receptor Inhibitors: Insights from Molecular Docking, ADME-Tox Prediction, DFT, and Molecular Dynamics
نویسندگان
1 Laboratoire de Chimie Physique, Université 8 Mai 1945, BP 401, Guelma 24000, Algeria
2 Laboratoire de Chimie Physique, Université 8 Mai 1945, BP 401, Guelma 24000, Algeria
3 Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques CRAPC-Bou-ismaïl, Tipaza, Algeria. Pharmaceutical Sciences Research Center -Ali Mendjeli-Constantine- 25000- Algeria
4 Laboratoire de Chimie Physique, Université 8 Mai 1945, BP 401, Guelma 24000, Algeria
5 Laboratoire de Chimie Physique, Université 8 Mai 1945, BP 401, Guelma 24000, Algeria
doi
10.22036/pcr.2025.525982.2687چکیده
— This study aims to explore five flavonoids derived from Algerian propolis, namely phytolarigenin (L1), pilosin (L2), ladanein (L3), chrysin (L4), and apigenin (L5), using computational tools to assess their antioxidant capacity and ability to inhibit human angiotensin-converting enzyme-2 (ACE2), a key target involved in SARS-CoV-2 entry. DFT calculations were performed to optimize molecular structures, analyze electronic descriptors, and evaluate antioxidant activity via HAT, SETPT, and SPLET mechanisms. Among the tested compounds, pilosin (L2) exhibited the highest antiradical potency, mainly attributed to its 8-OH group. Molecular docking revealed that all compounds had favorable interactions with the ACE2 active site, with binding scores ranging from -6.31 to -9.67 kcal/mol. Notably, pilosin (L2) demonstrated the most stable binding affinity (-9.67 kcal/mol), mainly due to a stable hydrogen bond involving its 8-OH group and Glu375 residue. Molecular dynamics simulations confirmed the structural stability of the L2/ACE2 complex over 100 ns. Additionally, pharmacokinetic predictions revealed good oral bioavailability and low toxicity for all molecules except L1, which showed a positive AMES test. These results strongly highlight pilosin (L2) as the leading dual-function candidate with potent antioxidant and antiviral properties, suitable for further drug development efforts.
