Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora

Jamil A. Shilpi, Mohammad Tuhin Ali, Sanjib Saha, Shihab Hasan, Alexander I. Gray, Veronique Seidel

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Abstract

There is an urgent need to discover and develop new drugs to combat Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans. In recent years, there has been a renewed interest in the discovery of new anti-TB agents from natural sources. In the present investigation, molecular docking studies were carried out on two ellagic acid derivatives, namely pteleoellagic acid (1) isolated from Ludwigia adscendens, and 3,3′-di-O-methyl ellagic acid 4-O-α-rhamnopyranoside (2) isolated from Trewia nudiflora, to investigate their binding to two enzymes involved in M. tuberculosis cell wall biogenesis, namely 2-trans-enoyl-ACP reductase (InhA) and β-ketoacyl-ACP reductase (MabA), and to pantothenate kinase (PanK type I) involved in the biosynthesis of coenzyme A, essential for the growth of M. tuberculosis. Molecular docking experiments were performed using AutoDock Vina. The crystal structures of InhA, MabA and PanK were retrieved from the RCSB Protein Data Bank (PDB). Isonicotinic-acyl-NADH for InhA and MabA, and triazole inhibitory compound for PanK, were used as references. Pteleoellagic acid showed a high docking score, estimated binding free energy of −9.4 kcal/mol, for the MabA enzyme comparable to the reference compound isonicotinic-acyl-NADH.Knowledge on the molecular interactions of ellagic acid derivatives with essential M. tuberculosis targets could prove a useful tool for the design and development of future anti-TB drugs.
Original languageEnglish
Number of pages7
JournalIn Silico Pharmacology
Volume3
Issue number10
DOIs
Publication statusPublished - 8 Dec 2015

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Onagraceae
Ellagic acid
Ellagic Acid
Mycobacterium tuberculosis
Enzymes
Derivatives
Tuberculosis
Coenzymes
Oxidoreductases
Molecular interactions
Acids
Biosynthesis
Free energy
Triazoles
Coenzyme A
Crystal structure
Cells
Pharmaceutical Preparations
Cell Wall
Proteins

Keywords

  • mycobacterium tuberculosis
  • ellagic acid derivatives
  • 2-trans-enoyl-ACP reductase (InhA)
  • patothenate kinase
  • PanK
  • Ludwigia adscendens
  • Trewia nudiflora

Cite this

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title = "Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora",
abstract = "There is an urgent need to discover and develop new drugs to combat Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans. In recent years, there has been a renewed interest in the discovery of new anti-TB agents from natural sources. In the present investigation, molecular docking studies were carried out on two ellagic acid derivatives, namely pteleoellagic acid (1) isolated from Ludwigia adscendens, and 3,3′-di-O-methyl ellagic acid 4-O-α-rhamnopyranoside (2) isolated from Trewia nudiflora, to investigate their binding to two enzymes involved in M. tuberculosis cell wall biogenesis, namely 2-trans-enoyl-ACP reductase (InhA) and β-ketoacyl-ACP reductase (MabA), and to pantothenate kinase (PanK type I) involved in the biosynthesis of coenzyme A, essential for the growth of M. tuberculosis. Molecular docking experiments were performed using AutoDock Vina. The crystal structures of InhA, MabA and PanK were retrieved from the RCSB Protein Data Bank (PDB). Isonicotinic-acyl-NADH for InhA and MabA, and triazole inhibitory compound for PanK, were used as references. Pteleoellagic acid showed a high docking score, estimated binding free energy of −9.4 kcal/mol, for the MabA enzyme comparable to the reference compound isonicotinic-acyl-NADH.Knowledge on the molecular interactions of ellagic acid derivatives with essential M. tuberculosis targets could prove a useful tool for the design and development of future anti-TB drugs.",
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Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora. / Shilpi, Jamil A.; Ali, Mohammad Tuhin; Saha, Sanjib; Hasan, Shihab; Gray, Alexander I.; Seidel, Veronique.

In: In Silico Pharmacology, Vol. 3, No. 10, 08.12.2015.

Research output: Contribution to journalArticle

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T1 - Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora

AU - Shilpi, Jamil A.

AU - Ali, Mohammad Tuhin

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AU - Gray, Alexander I.

AU - Seidel, Veronique

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KW - 2-trans-enoyl-ACP reductase (InhA)

KW - patothenate kinase

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KW - Ludwigia adscendens

KW - Trewia nudiflora

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