Antimycobacterial Activity of Bioactive Compounds from Eucalyptus globulus against Mycobacterium tuberculosis Aspartate-semialdehyde Dehydrogenase: In silico Analysis

Background Tuberculosis is the leading cause of death from a single infectious agent worldwide. Tuberculosis accounted for around 1.25 million deaths globally in 2023. The rise of Multidrug-resistant tuberculosis and the reported side effects of these available anti-TB drugs has complicated the control of the disease. This highlights the urgent need to discover and develop safer and more effective therapies for tuberculosis. Eucalyptus globulus is a tree widely distributed across tropical and subtropical regions with numerous medicinal benefits. Results The antimycobacterial potential of Eucalyptus globulus against Mycobacterium tuberculosis Aspartate-semialdehyde dehydrogenase (ASADH); an enzyme responsible for the bacterium’s growth and virulence was accessed using in silico studies. Fifteen bioactive compounds from Eucalyptus globulus were selected based on literature. Isoniazid; a first line anti-TB drug was used as our control. SwissADME online server was used to evaluate pharmacokinetic properties of the compounds. The compounds were further prepared to obtain the best docking poses using LigPrep module in the Maestro’s Schrodinger software. The compounds were docked into the protein's active site using Schrödinger's Maestro software’s Glide module and the resulting protein-ligand complexes was studied. Drug-likeness screening showed that only M-cymene violated Lipinski’s rule. Molecular docking revealed that thymol (-5.445) and sabinyl acetate (-5.097) has a higher docking score than isoniazid (-5.040), indicating a better binding affinity and biological activity against the target compared to the control (-5.040). Hydrogen bonds interaction of suggesting high strength of binding and molecular interactions that occurred between the protein-ligand complexes suggesting a strong antimycobacterial inhibitory effect. Conclusions In silico analysis from this study identifies thymol and sabinyl acetate from Eucalyptus globulus as promising candidates for further development as anti-TB treatments and show better docking with the target protein compared to isoniazid.