An in silico evaluation of anthraquinone derivatives as potential inhibitors of DNA gyrase B of Mycobacterium tuberculosis

The World Health Organization reported that tuberculosis remains on the list of the top ten threats to public health worldwide. Among the main causes is the limited effectiveness of treatments due to the emergence of a diverse spectrum of resistant strains of Mycobacterium tuberculosis, the causative agent of the disease. One of the main drug targets studied to combat M. tuberculosis is DNA gyrase, the only enzyme responsible for regulating DNA topology in this specie and considered essential in all bacteria. In this context, the present work tested the ability of 2,824 anthraquinones retrieved from the PubChem database to act as competitive inhibitors through interaction with ATP-binding pocket of DNA gyrase B of M. tuberculosis. Virtual screening results based on molecular docking identified 7122772 (N-(2-hydroxyethyl)-9,10-dioxoanthracene-2-sulfonamide) as the best-scored ligand. From this anthraquinone, a new derivative was designed harbouring an aminotriazole moiety, which exhibited higher binding energy calculated by molecular docking scoring and free energy calculation from molecular dynamics simulations. In addition, in these last analyses, this ligand showed to be stable in complex with the enzyme and further predictions indicated an acceptable pharmacokinetic profile. Taken together, the presented results show a new anthraquinone synthetically accessible and with promising potential to inhibit the GyrB of M. tuberculosis.