title: Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Natural Products Research Laboratories, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.|Pharmacy Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
authors.forename: Jamil A
authors.initials: JA
authors.lastname: Shilpi
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Mohammad Tuhin
authors.initials: MT
authors.lastname: Ali
authors.affiliation: Pharmacy Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Saha
authors.affiliation: Bioinformatics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Shihab
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Natural Products Research Laboratories, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Gray
authors.affiliation: Natural Products Research Laboratories, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. veronique.seidel@strath.ac.uk.
authors.forename: Véronique
authors.initials: V
authors.lastname: Seidel
keywords: 2-trans-enoyl-ACP reductase (InhA); Ellagic acid derivatives; Ludwigia adscendens; Mycobacterium tuberculosis; Pantothenate kinase (PanK); Trewia nudiflora; β-ketoacyl-ACP reductase (MabA)
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