Computational Investigation of Isoxazole‐Based Molecules as Potential Drug‐Resistant Anti‐Tuberculosis H37Rv.

Abstract Investigation of new active therapeutic drugs against the emerging drug‐resistant Mycobacterium tuberculosis is a current medical and health challenge. Based on previously reported isoxazole‐based molecules that have a potent effect against Mycobacterium tuberculosis, computational methods were used in the current study to investigate the effect of isoxazole‐based molecules as a potential active drug‐resistant drug Mycobacterium tuberculosis H37Rv. Molecular models of isoxazole‐based molecules were established by 3D‐QSAR study, and different results were interpreted to propose 6 candidate agents more active than the previously reported compounds in the literature. Also, the candidate structures are more active than the therapeutic drug agent Isoniazid (NIH) against Mycobacterium Tuberculosis. Evaluation of the synthetic accessibility coefficient and the Lipinski properties of newly designed agent candidates indicate that these agents meet the criteria of a drug according to the Lipinski and Veber rules because they can be synthesized. In‐silico evaluation of ADMETox properties shows satisfactory results for most newly designed agent candidates. According to molecular docking, the drug candidates have a high score with a stable docked pose in the receptor (PDB code: 5v3y) compared to Isoniazid (NIH). The DFT and molecular dynamics study confirmed the previous results of 3D‐QSAR and molecular docking models.