Molecular Docking, Molecular Dynamics, pkCSM Drug‐Likeness Profiles, Toxicity, and DFT Study of the Antioxidant and Anticancer Activities of Three Flavonoid Derivatives

Abstract This work presents a theoretical study of the antioxidant and anticancer properties of three flavonoid derivatives Isoquercitin, Ophioglonol, and Quercetin. DFT calculations were performed to analyze their electronic properties, providing insights into their reactivity and mechanism of action. Molecular docking and molecular dynamics simulations were conducted to examine the stability behavior of the protein‐ligand complexes, providing a detailed mechanism of the interactions at the atomic level. Additionally, some physicochemical and pharmacokinetic predictions were examined by using several web servers. Quercetin and isoquercetin show therapeutic properties, with MESP plots revealing interaction regions with SOD and hAPN targets. However, isoquercetin raises concerns related to AMES toxicity and hERG inhibition. The results of Molecular docking and MD simulations provide theoretical guidance for developing effective inhibitors to treat cancer, but further experimental validation is needed to optimize therapeutic efficacy. The MM/GBSA show that Ophioglonol has the strongest binding affinity with the protein, driven by many interactions. The Actionon also demonstrates strong binding, while Isoquercitin and Quercetin have moderate to weaker affinities. The PCA revealed distinct conformational changes in the protein upon binding with the ligand, highlighting specific regions of flexibility, which could be crucial for understanding their binding mechanisms and potential therapeutic effects.