Affiliation:
1. Federal University of Agriculture Abeokuta
2. University of Ghana
Abstract
Abstract
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 their violation of Lipinski's, Ghose's, Veber's, Egan's, or Muegge's rules. Interestingly, the remaining thirteen compounds showed stronger binding affinities with InhA than those of the control drugs, depicting them as potential anti-tuberculosis 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. Also, the compounds exhibited hydrogen bonds, hydrophobic, and π stacking interactions with the active site residues of the protein; hence, contributing to their potential as antituberculosis agents. The ADMET property of each of the hit ligands predicted its ability to effectively reach and remain at the target protein to exert its therapeutic influence. The study depicts that the screened bioactive compounds exhibited more favorable docking interactions with the target protein than the control drugs, potentially contributing to tuberculosis treatment.
Publisher
Research Square Platform LLC