Identification of Potent Hepcidin Antagonists for Anemia Treatment: An In Silico Drug Repositioning Study
نویسندگان
1 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco
2 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco
3 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco
4 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco
5 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco
doi
10.22036/pcr.2025.498178.2624چکیده
Iron deficiency anemia is a global health issue lacking effective solutions. Believing that drug repurposing offers potential benefits by leveraging existing drugs, this study aims to identify existing drugs that could be repurposed for treating iron deficiency anemia through inhibiting the biological activity of hepcidin, a key iron regulatory protein. To achieve this objective, molecular docking studies were performed to screen 58 randomly chosen FDA-approved drugs against the hepcidin protein. Four drugs were found to have the strongest binding affinities for hepcidin, namely Apixaban, Celecoxib, Sulfasalazine, and Fexofenadine, suggesting their possible repurposing for the treatment of iron deficiency anemia. They formed favorable interactions within the hepcidin binding site, including hydrogen bonds and hydrophobic contacts. Furthermore, the molecular dynamics of the complexes formed between the best selected ligands and the biological target was simulated for 100 ns to study their dynamic behavior and evaluate their stability in an aqueous medium. The obtained results affirm the stability of the complexes formed during the molecular recognition between the selected ligands and hepcidin. The current investigation revealed useful outcomes that could help accelerate the discovery of new therapies for iron deficiency anemia.
