Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2′-N-acetyltransferase in Mycobacterium tuberculosis

•The Anti-tuberculosis activity of Andrographis paniculata was screened using Luciferase Reporter Phage Assay (LRP).•Based on the bioassay guided fractionation, Andrographolide has been identified as an active molecule.•The probable drug target for Andrographolide was identified by using docking analysis.•Molecular simulation was performed to refine the target—drug complex.

Tuberculosis (TB) still remains a major challenging infectious disease. The increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-TB drugs. Antimycobacterial activity of Andrographis paniculata was evaluated using a rapid LRP assay and the probable targets were identified by docking analysis. The methanolic extract of A. paniculata showed maximum antimycobacterial activity at 250 μg/ml against all the tested strains of M. tuberculosis (H37Rv, MDR, and drug sensitive). Based on bioassay guided fractionation, andrographolide was identified as the potent molecule. With the docking analysis, both ICDH (Isocitrate Dehydrogenase) and AAC (Aminoglycoside 2′-N-acetyltransferase) were predicted as targets of andrographolide in M. tuberculosis. Molecular simulation revealed that, ICDH showed low binding affinity to andrographolide. However, for AAC, the andrographolide was observed to be well within the active site after 10 ns of molecular simulation. This suggests that ACC (PDB ID 1M4I) could be the probable target for andrographolide.

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