<em style="mso-bidi-font-style: normal;"><span lang="EN">In Silico<span lang="EN"> Identification of RAD۵۱ Inhibitors Derived from Evodia suaveolens as Novel Therapeutic Candidates for Human Leukemia

Leukemia remains a major global health burden, with acute myeloid leukemia (AML) recognized as one of its most aggressive forms. The overexpression of RAD۵۱, a key protein in homologous recombination-mediated DNA repair, has been linked to genomic instability and treatment resistance in AML, thereby reinforcing the need for novel therapeutic strategies targeting this pathway. This study investigates the potential inhibitory activity of bioactive compounds from Evodia suaveolens against the RAD۵۱ protein using an in silico approach. Ten phytochemical compounds identified from E. suaveolens leaf extracts were evaluated through ADMET profiling and molecular docking against RAD۵۱ (PDB ID: ۱N۰W). Docking results show that lanosterol and obtusifoliol exhibit the highest binding affinity (–۷.۷ kcal/mol), followed by stigmasterol and β-sitosterol (–۷.۶ kcal/mol). These compounds form dominant interactions with key residues THR۲۹۷, TYR۳۱۵, and ASP۳۱۶ located within the ATPase domain, which plays a pivotal role in RAD۵۱ filament formation. ADMET evaluation and physicochemical assessment indicate that all compounds possess a molecular weight below ۵۰۰ g/mol and an optimal number of hydrogen bond donors and acceptors, although several sterol derivatives violate the lipophilicity parameter (MLogP > ۵). Evodone demonstrates the most favorable pharmacokinetic profile, balancing solubility and permeability. Overall, sterol and triterpenoid compounds from Evodia suaveolens show potential as RAD۵۱ inhibitors with promising anti-leukemia activity. However, formulation optimization is required to address limitations in water solubility.

کلیدواژه ها:

Evodia suaveolens ، RAD۵۱ ، Molecular docking ، AML ، In silico ، ADMET