The bacteria Mycobacterium tuberculosis is responsible for the pathology known as tuberculosis, which is one of the top 10 causes of death in the world, according to the World Health Organization (WHO) in 2017 about 10 million people contracted the disease, of which 1.6 million died last year. The bacterial infection in its primary form compromises the lungs, however, it is possible to reach the brain, bones, heart, kidneys and other organ of the human body. The form of transmission is mainly through the air, where infected people cough, sneeze or spit spreading the bacteria, leaving it available to contaminate new individuals. Tuberculosis is treatable with the aid of antibiotics and avoided from childhood with the aid of the vaccine BCG (Bacillus Calmette-Guérin), however, studies show that 82% of tuberculosis cases the bacterium develops resistance to first-line drugs such as rifampicin, due to this problem, research in the field of pharmaceutical sciences is necessary to make new bioactive available to treat the disease. Some authors have developed studies on the use of nucleoside / nucleotide analogues as antitubercular bioactive and have shown good results that have made this class of synthetic compounds promising drug candidates in the fight against M. tuberculosis. Knowing the potential activity against tuberculosis of nucleotides, the objective of this study is the molecular modeling with the use of several computational tools for the theoretical proposition of some derivatives of 2,5-dihidroxyfuran-2,5-diol with adenine against tuberculosis-causing bacteria. For the initial part of this research, a model of activity prediction was developed in the KNIME Analytics Platform 3.7 using molecules exported from the database of chemical structure ChEMBL (https://www.ebi.ac.uk/chembl), thus, nucleotides that were active against the model were subjected to a virtual screening, taking into consideration the risks of cytotoxicity (mutagenicity, carcinogenicity, skin irritability and effect on the reproductive system), oral absorption rate (%ABS) and Lipinski's rule, of the compounds approved in the screening performed were calculated the energies of the ligand-receptor interactions for the proteins (PDB ID 5VRN and PDB ID 5YHV), as well as the drugs used as controls: pyrazinamide, ethambutol, rifabutin, amikacin, levofloxacin, ethionamide and protionamide. As conclusion of this research, it was possible to perceive the existence of compounds approved by the virtual screening that presented good ligand-receptor interactions in the molecular docking for the two proteins selected, being the most promising ones of the studied series.
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MOLECULAR MODELING OF NUCLEOTIDE DERIVATIVES OF 2.5-DIHYDROFURAN-2,5-DIOL FOR EVALUATION OF POTENTIAL ANTITUBERCULAR ACTIVITY
Published: 16 December 2018 by MDPI in MOL2NET'18, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 4th ed. congress USEDAT-04: USA-Europe Data Analysis Training Program Workshop, Cambridge, UK-Bilbao, Spain-Miami, USA, 2018
Keywords: Molecular docking; tuberculosis; in silico; nucleotide; virtual screening.