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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 THN; different views of the THN interactions involved at the active sites in glutathione. (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 009: Docking interactions of THN; different views of the THN interactions involved at the active sites in glutathione. (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.

Mentions: A docking study comparison was made between lawsone and THN for the GSH receptor interaction. Significant variations were observed in the affinity of THN for GSH with respect to binding energy (─ 5.43 kcal/mol-1), ligand efficiency (─ 0.42 kcal/mol-1), intermolecular energy (─ 5.85 kcal/mol-1), van der Waal force (5.78 kcal/mol-1), total intermolecular energy (─ 0.40 kcal/mol-1) and RMSD (80.74 kcal/mol-1), THN shows a dominant molecular interaction with the GSH receptor. Through the positional affinities of OH, 2-hydroxy (= OH) and 4-hydroxy (= OH) of THN for amino acids, their molecular affinities for aspartine, serine and arginine were predicted. The results are as follows: 1 OH with aspartine oxygen at 3.0 kcal/mol-1, 2-hydroxy with serine oxygen at 2.4, 2.6 and 3.0 kcal/mol-1, and 4-hydroxy with arginine oxygen and nitrogen at 2.9 and 3.2 kcal/mol-1, respectively. The results in Figs. 8,9 show that the additional amino acids interactions were found and analyzed for the 1-OH and 4-hydroxy (= OH) positions of THN with nitrogen atoms of aspartine (2.8 kcal/mol-1), thrionine (3.4 kcal/mol-1) and histidine (2.8 kcal/mol-1).


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 THN; different views of the THN interactions involved at the active sites in glutathione. (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 009: Docking interactions of THN; different views of the THN interactions involved at the active sites in glutathione. (a) The yellow dotted lines indicate the presence of hydrogen-bond interactions. (b) Binding energy and binding reaction graphical tool.
Mentions: A docking study comparison was made between lawsone and THN for the GSH receptor interaction. Significant variations were observed in the affinity of THN for GSH with respect to binding energy (─ 5.43 kcal/mol-1), ligand efficiency (─ 0.42 kcal/mol-1), intermolecular energy (─ 5.85 kcal/mol-1), van der Waal force (5.78 kcal/mol-1), total intermolecular energy (─ 0.40 kcal/mol-1) and RMSD (80.74 kcal/mol-1), THN shows a dominant molecular interaction with the GSH receptor. Through the positional affinities of OH, 2-hydroxy (= OH) and 4-hydroxy (= OH) of THN for amino acids, their molecular affinities for aspartine, serine and arginine were predicted. The results are as follows: 1 OH with aspartine oxygen at 3.0 kcal/mol-1, 2-hydroxy with serine oxygen at 2.4, 2.6 and 3.0 kcal/mol-1, and 4-hydroxy with arginine oxygen and nitrogen at 2.9 and 3.2 kcal/mol-1, respectively. The results in Figs. 8,9 show that the additional amino acids interactions were found and analyzed for the 1-OH and 4-hydroxy (= OH) positions of THN with nitrogen atoms of aspartine (2.8 kcal/mol-1), thrionine (3.4 kcal/mol-1) and histidine (2.8 kcal/mol-1).

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