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Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene.

Gopal V, Al Rashid MH, Majumder S, Maiti PP, Mandal SC - J Pharmacopuncture (2015)

Bottom Line: The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM(+) followed by a semi-empirical (PM3) method.Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids.Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

View Article: PubMed Central - PubMed

Affiliation: Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.

ABSTRACT

Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4.

Methods: The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM(+) followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of 54 × 55 × 56, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10.

Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids.

Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

No MeSH data available.


Related in: MedlinePlus

Docking interactions of lawsone; different views of the lawsone interactions involved at the active sites in glutathione reductase (GR). (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.
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Figure 010: Docking interactions of lawsone; different views of the lawsone interactions involved at the active sites in glutathione reductase (GR). (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.

Mentions: The GR interaction was investigated for another protein affinity evaluation for lawsone and THN. The four docking parameters, binding energy, ligand efficiency, intermolecular energy and van der Waal force showed almost one and the same interactions of lawsone and THN with protein GSH reductase: ─ 5.12, ─ 0.39, ─ 5.11, and ─ 5.06 kcal/ mol-1 for lawsone and ─ 5.17, ─ 0.40, ─ 5.52, and ─ 5.38 kcal/mol-1 for THN, respectively. The electrostatic energy and the total intermolecular energy showed the leading molecular interactions for THN rather than for lawsone: ─ 0.14 and ─ 0.48 kcal/mol-1, respectively. The 2-hydroxy position of lawsone interacted with the one mole oxygen of valine and one mole hydrogen of threonine: 2.2 and 3.0 kcal/mol-1, respectively. In the case of THN amino acid interactions, one-hydroxy had high affinities for the nitrogen and the oxygen of glycine (2.8 kcal/mol-1), two-hydroxy had a high affinity for the oxygen of glycine (2.9 kcal/mol-1), and four-hydroxyl had a high affinity for proline oxygen (2.8 kcal/mol-1) (Figs. 10,11).


Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene.

Gopal V, Al Rashid MH, Majumder S, Maiti PP, Mandal SC - J Pharmacopuncture (2015)

Docking interactions of lawsone; different views of the lawsone interactions involved at the active sites in glutathione reductase (GR). (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481394&req=5

Figure 010: Docking interactions of lawsone; different views of the lawsone interactions involved at the active sites in glutathione reductase (GR). (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.
Mentions: The GR interaction was investigated for another protein affinity evaluation for lawsone and THN. The four docking parameters, binding energy, ligand efficiency, intermolecular energy and van der Waal force showed almost one and the same interactions of lawsone and THN with protein GSH reductase: ─ 5.12, ─ 0.39, ─ 5.11, and ─ 5.06 kcal/ mol-1 for lawsone and ─ 5.17, ─ 0.40, ─ 5.52, and ─ 5.38 kcal/mol-1 for THN, respectively. The electrostatic energy and the total intermolecular energy showed the leading molecular interactions for THN rather than for lawsone: ─ 0.14 and ─ 0.48 kcal/mol-1, respectively. The 2-hydroxy position of lawsone interacted with the one mole oxygen of valine and one mole hydrogen of threonine: 2.2 and 3.0 kcal/mol-1, respectively. In the case of THN amino acid interactions, one-hydroxy had high affinities for the nitrogen and the oxygen of glycine (2.8 kcal/mol-1), two-hydroxy had a high affinity for the oxygen of glycine (2.9 kcal/mol-1), and four-hydroxyl had a high affinity for proline oxygen (2.8 kcal/mol-1) (Figs. 10,11).

Bottom Line: The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM(+) followed by a semi-empirical (PM3) method.Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids.Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

View Article: PubMed Central - PubMed

Affiliation: Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.

ABSTRACT

Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4.

Methods: The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM(+) followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of 54 × 55 × 56, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10.

Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids.

Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

No MeSH data available.


Related in: MedlinePlus