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<p>Tuberculosis (TB) is a significant global public health challenge. Targeting enoyl-acyl carrier protein (ACP) reductase (InhA), an enzyme involved in mycolic acid biosynthesis, is a promising path to discovering an effective treatment for tuberculosis. This study assessed the inhibitory potential of bioactive compounds from four medicinal plants (<i>Garcinia kola</i>, <i>Moringa oleifera</i>, <i>Newbouldia laevis</i>, and <i>Ocimum gratissimum</i>) and control drugs (Isoniazid and Ethionamide) against InhA. Molecular docking and computational tools were used to evaluate the binding affinities and interactions with InhA’s active site. Drug-likeness, binding affinities, bioactivity, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) attributes were determined using online tools. Ten out of twenty-three bioactive compounds studied were screened out due to violating Lipinski’s, Ghose’s, Veber’s, Egan’s, or Muegge’s rules. The remaining thirteen compounds showed stronger binding affinities with InhA than the control drugs. The binding energy of the bioactive compounds ranged from − 8.0 to −&#xa0;9.5&#xa0;kcal/mol, while those of Isoniazid and Ethionamide were 6.1&#xa0;kcal/mol and − 6.0&#xa0;kcal/mol, respectively. The compounds also exhibited hydrogen bonds, hydrophobic, and π stacking interactions with the protein residues. Molecular dynamic simulations confirmed that 5,7-dihydroxydehydroiso-α-lapachone had a compact and more stable complex with InhA than the hit ligands with high binding energies. The ADMET property of each hit ligand predicted its ability to effectively reach and remain at the target protein to exert its therapeutic influence. The study shows that the screened bioactive compounds, especially 5,7-dihydroxydehydroiso-α-lapachone, exhibit drug-like properties capable of inhibiting InhA, hence, could serve as a novel anti-tuberculosis drug.</p>

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Molecular docking and pharmacokinetic studies of bioactive compounds from medicinal plants as promising inhibitory agents against Mycobacterium tuberculosis enoyl-acyl carrier protein (ACP)-reductase (InhA)

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • O. O. Fawibe,
  • B. R. Lawal,
  • A. A. Mustafa,
  • A. S. Oyelakin,
  • O. F. Akinyemi,
  • A. O. Bankole,
  • S. A. Poku,
  • F. Boudou,
  • D. Das

摘要

Tuberculosis (TB) is a significant global public health challenge. Targeting enoyl-acyl carrier protein (ACP) reductase (InhA), an enzyme involved in mycolic acid biosynthesis, is a promising path to discovering an effective treatment for tuberculosis. This study assessed the inhibitory potential of bioactive compounds from four medicinal plants (Garcinia kola, Moringa oleifera, Newbouldia laevis, and Ocimum gratissimum) and control drugs (Isoniazid and Ethionamide) against InhA. Molecular docking and computational tools were used to evaluate the binding affinities and interactions with InhA’s active site. Drug-likeness, binding affinities, bioactivity, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) attributes were determined using online tools. Ten out of twenty-three bioactive compounds studied were screened out due to violating Lipinski’s, Ghose’s, Veber’s, Egan’s, or Muegge’s rules. The remaining thirteen compounds showed stronger binding affinities with InhA than the control drugs. The binding energy of the bioactive compounds ranged from − 8.0 to − 9.5 kcal/mol, while those of Isoniazid and Ethionamide were 6.1 kcal/mol and − 6.0 kcal/mol, respectively. The compounds also exhibited hydrogen bonds, hydrophobic, and π stacking interactions with the protein residues. Molecular dynamic simulations confirmed that 5,7-dihydroxydehydroiso-α-lapachone had a compact and more stable complex with InhA than the hit ligands with high binding energies. The ADMET property of each hit ligand predicted its ability to effectively reach and remain at the target protein to exert its therapeutic influence. The study shows that the screened bioactive compounds, especially 5,7-dihydroxydehydroiso-α-lapachone, exhibit drug-like properties capable of inhibiting InhA, hence, could serve as a novel anti-tuberculosis drug.