Prospection of Therapeutic Agents Targeting Aurora Kinase, a Protein in the Treatment of Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is characterized by an imbalance in the production and development of hematopoietic lymphoid cells, a malignant disease capable of affecting the proliferation-selection of hematopoietic cells. The Aurora kinase A protein participates in several steps of the mitosis process. Its deregulation can trigger the process of carcinogenesis, which has become a therapeutic target of interest for computational prediction and the development of inhibitory drugs. Studies report its overexpression in malignant cells of patients with ALL. Objective: The present study aims to prospect new molecules to identify a potential inhibitor of Aurora kinase A for the pharmaceutical market. Methodology: Virtual screening and molecular docking study was performed using the MCULE and DockThor web servers. The pharmacodynamic and pharmacokinetic profile of the molecules were evaluated using the Swiss ADME and ProTox-II programs were used. Results: Ten molecules were identified by virtual screening, in which only two, MCULE-349 and MCULE-796, showed the best score, binding, at the site of action of the protein, interacting positively with amino acids, lipid-soluble molecules with low toxicity and with violation of only 1 Lipinski rule. Conclusion: Both molecules interact with the site of action, acting as inhibitors or blockers of the catalytic site, becoming potential Aurora kinase A inhibitors and anticancer molecules.