| Autor: |
Amorim JC; Academic Unit of Health and Wellness, Catholic University of Cuenca, Cuenca 010105, Ecuador., Cabrera Bermeo AE; Academic Unit of Health and Wellness, Catholic University of Cuenca, Cuenca 010105, Ecuador., Vásquez Urgilés VE; Academic Unit of Health and Wellness, Catholic University of Cuenca, Cuenca 010105, Ecuador., Martínez León MR; Academic Unit of Health and Wellness, Catholic University of Cuenca, Cuenca 010105, Ecuador., Carpio Arévalo JM; Academic Unit of Health and Wellness, Catholic University of Cuenca, Cuenca 010105, Ecuador. |
| Jazyk: |
angličtina |
| Zdroj: |
Microorganisms [Microorganisms] 2022 Dec 08; Vol. 10 (12). Date of Electronic Publication: 2022 Dec 08. |
| DOI: |
10.3390/microorganisms10122434 |
| Abstrakt: |
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 resistant strains of Mycobacterium tuberculosis . 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 2824 anthraquinones retrieved from the PubChem database to act as competitive inhibitors through interaction with the 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 a low probability of cytotoxic and off-target effects, as well as an acceptable pharmacokinetic profile. Taken together, the presented results show a new synthetically accessible anthraquinone with promising potential to inhibit the GyrB of M. tuberculosis . |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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