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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 1,2,4-trihydroxynaphthalen (THN); different views of the THN interactions involved at the active sites in nitric oxide synthase. (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 005: Docking interactions of 1,2,4-trihydroxynaphthalen (THN); different views of the THN interactions involved at the active sites in nitric oxide synthase. (a) The yellow dotted lines indicate the presence of hydrogen bond interactions. (b) Binding energy and binding reaction graphical tool.

Mentions: The NOS protein was chosen, and the docking binding energy of lawsone energy for NOS was found to be 11.55 kcal/mol-1; that for THN was found to be ─ 6.76 kcal/mol-1. The latter result was confirmed through the major docking parameters: an intermolecular energy of ─ 7.16, a van der Wall force of ─ 7.03, an electrostatic energy of ─ 0.13, and a total internal energy 0.42, with all values being in units of kcal/mol-1. The positional affinities of one hydroxy (OH) of THN was identified for a proline oxygen atom, a leucine nitrogen atom, and a glycine nitrogen atom 3.3 kcal/mol-1, 3.2 kcal/mol-1 and 3.3 kcal/mol-1, respectively. The 2-hydroxy of THN shows amino acid sites that have an affinities for glycine nitrogen, proline oxygen and leucine oxygen: 2.7, 2.9, 3.2 and 3.3 kcal/mol-1, respectively (Figs. 4,5).


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 1,2,4-trihydroxynaphthalen (THN); different views of the THN interactions involved at the active sites in nitric oxide synthase. (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 005: Docking interactions of 1,2,4-trihydroxynaphthalen (THN); different views of the THN interactions involved at the active sites in nitric oxide synthase. (a) The yellow dotted lines indicate the presence of hydrogen bond interactions. (b) Binding energy and binding reaction graphical tool.
Mentions: The NOS protein was chosen, and the docking binding energy of lawsone energy for NOS was found to be 11.55 kcal/mol-1; that for THN was found to be ─ 6.76 kcal/mol-1. The latter result was confirmed through the major docking parameters: an intermolecular energy of ─ 7.16, a van der Wall force of ─ 7.03, an electrostatic energy of ─ 0.13, and a total internal energy 0.42, with all values being in units of kcal/mol-1. The positional affinities of one hydroxy (OH) of THN was identified for a proline oxygen atom, a leucine nitrogen atom, and a glycine nitrogen atom 3.3 kcal/mol-1, 3.2 kcal/mol-1 and 3.3 kcal/mol-1, respectively. The 2-hydroxy of THN shows amino acid sites that have an affinities for glycine nitrogen, proline oxygen and leucine oxygen: 2.7, 2.9, 3.2 and 3.3 kcal/mol-1, respectively (Figs. 4,5).

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