فهرست نشریات علمی دسترسی آزاد ایران

Colorectal cancer poses a significant global health challenge, driving demand for innovative therapeutic strategies. Apoptosis, modulated by the key anti-apoptotic regulator Bcl-xL, serves as a critical target for selective elimination of cancer cells and overcoming survival mechanisms. This study investigated the molecular action of magnolialide, a natural compound derived from Magnolia grandiflora, as a potential anti-colorectal cancer agent through its interaction with Bcl-xL (protein ID: 3QKD) using integrated computational methods. Molecular docking analysis revealed magnolialide’s superior binding affinity (-7.65 kcal/mol) and optimal orientation at the 3QKD active site compared to 5FU (-3.58 kcal/mol). Dynamics simulations conducted over 100 ns confirmed sustained stability and consistent molecular interactions, reinforcing the reliability of the binding. ADMET profiling indicated favorable pharmacokinetics for magnolialide, featuring high intestinal absorption, moderate distribution, and minimal metabolic interference, despite a lower maximum tolerated dose compared to 5FU. Toxicity assessments showed no mutagenic potential, further supporting its safety profile. DFT analysis revealed enhanced molecular reactivity for magnolialide (ΔE = 11.6296 eV) compared to 5FU (ΔE = 12.5089 eV), attributed to the smaller energy gap indicating greater electron transition potential. These findings establish magnolialide as a promising candidate for colorectal cancer therapy via Bcl-xL-mediated apoptosis modulation.