title: Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
authors.forename: Amudha
authors.initials: A
authors.lastname: Prabu
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Hassan
authors.affiliation: Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
authors.lastname: Prabuseenivasan
authors.affiliation: Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
authors.forename: A S
authors.initials: AS
authors.lastname: Shainaba
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India.
authors.forename: L E
authors.initials: LE
authors.lastname: Hanna
authors.affiliation: Centre for Drug Discovery and Development, Sathyabama University, Chennai 600119, India. Electronic address: vanaja_kumar51@yahoo.co.in.
authors.forename: Vanaja
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020816:Amino Acid Motifs; D035685:Andrographis / Q000737:chemistry*; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010936:Plant Extracts / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004224:Diterpenes; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C030419:andrographolide; D007521:Isocitrate Dehydrogenase; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase
keywords: Andrographolide; Antimycobacterial activity; Docking; Drug target; Molecular simulation; Tuberculosis