Tuberculosis (TB) is still a worldwide health problem caused, in large part, by mycobacterium tuberculosis (MTB). The urgent need for the discovery of new antitubercular (anti-TB) agents has revealed the activity of coumarin derivatives against MTB. Therefore, a serie of 36 coumarins derivates was used to evaluated their antitubercular activity in silico against three proteins of Mycobacterium tuberculosis, known as FadD32, wild type and mutant DNA gyrase. The compounds had their energies minimized. Calculations of molecular descriptors were performed to carry out chemometric study of CPCA, docking and molecular dynamics. Our results showed that the major influence is the amphiphilic character, with predominance of the hydrophilic character, which corroborated with the docking results in the cavity of the active site for proteins. In homology studies it has been observed that mutation changes contribute to protein destabilization and may interfere with compound activity. The Score values and the interactions for the three proteins of the study were also favorable, evidencing the promising activity of coumarins derivatives antitb. We observed that the greatest divergence of interactions occurred for GyrA, whereas for GyrB the mutations did not influence the interaction of coumarins. In molecular dynamics studies showed similar degree of instability the ligand pdb and coumarin, showing that certain residues are involved in the conformational alteration of the protein. Therefore, we conclude that the lead compound 2c showed potentiality of the coumarin derivative class as new candidate antituberculosis.