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J Mol Graph Model. 2015 Sep;61:133-40. doi: 10.1016/j.jmgm.2015.07.001. Epub 2015 Jul 21.

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

Author information

1
Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
2
Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
3
Centre for Drug Discovery and Development, Sathyabama University, Chennai 600119, India. Electronic address: vanaja_kumar51@yahoo.co.in.

Abstract

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 250μg/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 10ns of molecular simulation. This suggests that ACC (PDB ID 1M4I) could be the probable target for andrographolide.

KEYWORDS:

Andrographolide; Antimycobacterial activity; Docking; Drug target; Molecular simulation; Tuberculosis

PMID:
26245695
DOI:
10.1016/j.jmgm.2015.07.001
[Indexed for MEDLINE]

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