Docking-Based Virtual Screening and Molecular Dynamics Simulations of Quercetin Analogs as Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors of Mycobacterium tuberculosis

The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl...

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Veröffentlicht in:Scientia pharmaceutica Jg. 89; H. 2; S. 20
Hauptverfasser: Pitaloka, Dian Ayu Eka, Ramadhan, Dwi Syah Fitra, Arfan, Chaidir, Lidya, Fakih, Taufik Muhammad
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel MDPI AG 01.06.2021
Schlagworte:
Amino acids
Binding sites
Drug resistance
dynamic simulation
Enzymes
Fatty acids
Flavonoids
Hydrogen bonds
isoniazid
Ligands
Multidrug resistant organisms
multidrug-resistant tuberculosis
Principal components analysis
Proteins
quercetin
Simulation
Solvents
Tuberculosis
virtual screening
ISSN:2218-0532, 0036-8709, 2218-0532
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Zusammenfassung:The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl-carrier-protein] reductase (InhA), which controls mycobacterial cell wall construction. Initially, 391 quercetin analogs present in the KNApSAck_3D database were selected, filters were sequentially applied by docking-based virtual screening. After recategorizing the variables (bond energy prediction and molecular interaction, including hydrogen bond and hydrophobic bond), compounds C00013874, C00006532, and C00013887 were selected as hit ligands. These compounds showed great hydrophobic contributions, and for each hit ligand, 100 ns of molecular dynamic simulations were performed, and the binding free energy was calculated. C00013874 demonstrated the greatest capacity for the InhA enzyme inhibition with ΔGbind = −148.651 kcal/mol compare to NAD (native ligand) presented a ΔGbind = −87.570 kcal/mol. These data are preliminary studies and might be a suitable candidate for further experimental analysis.
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content type line 14
ISSN:2218-0532
0036-8709
2218-0532
DOI:10.3390/scipharm89020020