Identification of novel compounds from Olea Europaea targeting hDus2 as potential anticancer agents: a molecular docking and molecular dynamics study

Introduction Leukemia, a type of blood cancer, ranks among the top causes of cancer-related fatalities. Human tRNA-dihydrouridine synthase 2 (hDus2) catalyzes the conversion of uridine to dihydrouridine in the tRNA and is overexpressed in cancer cells, facilitating the translational process required for cancer cell growth. Inhibition of hDus2 reduces cancer cell growth and viability while increasing apoptosis sensitivity under stress, making it an excellent cancer target. Olea Europaea is known to be abundant in flavonoids, polyphenols, vitamins, and antioxidants, and shows immense potential in providing health benefits. The varied properties of these compounds are very significant in the prevention of disorders such as Alzheimer’s and Cancer. Methodology Olea Europaea extract was tested for anti-cancer activity, followed by identification of potential leads using in silico methods. The compounds from the OliveNet database were screened against the hDus2 enzyme. The identified compounds were further validated using Molecular Dynamics (MD) Simulation. Results Molecular docking studies with the Glide module revealed that several compounds showed high affinity for hDus2. The top five compounds out of six hundred seventy six compounds were selected for molecular dynamics simulations to study their structural stability and conformational dynamics in the presence of solvent molecules. Conclusion Binding free energy calculations revealed that all complexes were stable, with P166 and P161 exhibiting the highest binding potential against hDus2. These findings lay the foundation for the development of novel anti-cancer therapeutics targeting leukemia.