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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

Molinspiration computational evaluations of the molecular properties and the bioactivity of lawsone.
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Figure 016: Molinspiration computational evaluations of the molecular properties and the bioactivity of lawsone.

Mentions: Lipophilicity and solubility are the key molecular properties in the absorption of drugs in a biological system. Used to predict the oral bioavailability of a drug, Lipinski’s rule of five (log P, molecular weight, number of atoms, number of hydrogen donors, number of hydrogen acceptors, number of violations, number of rotatable bonds) is considered in the drug discovery process. Computational application tools facilitate learning about the pharmacokinetic properties of individual drug molecules. Many changes and improvements have marked the area of medicinal chemistry, and new approaches to improve drug efficacy by use of technological resources have been developed. In Molinspiration, analyses of the different approaches by using computers are directed to the evaluation of chemistry and physical chemistry data that influences the pharmacokinetic properties of drugs. The molecular and bioactive properties of lawsone and THN are presented in Figs. 16,17 [14]. The selected ligands satisfy Lipinski’s rule of five as log p < 5, molecular weight < 500 g/mol, number of hydrogen bond acceptors < 10, number of hydrogen bond donors < 5 and number of rotatable bonds < 10.


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)

Molinspiration computational evaluations of the molecular properties and the bioactivity of lawsone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 016: Molinspiration computational evaluations of the molecular properties and the bioactivity of lawsone.
Mentions: Lipophilicity and solubility are the key molecular properties in the absorption of drugs in a biological system. Used to predict the oral bioavailability of a drug, Lipinski’s rule of five (log P, molecular weight, number of atoms, number of hydrogen donors, number of hydrogen acceptors, number of violations, number of rotatable bonds) is considered in the drug discovery process. Computational application tools facilitate learning about the pharmacokinetic properties of individual drug molecules. Many changes and improvements have marked the area of medicinal chemistry, and new approaches to improve drug efficacy by use of technological resources have been developed. In Molinspiration, analyses of the different approaches by using computers are directed to the evaluation of chemistry and physical chemistry data that influences the pharmacokinetic properties of drugs. The molecular and bioactive properties of lawsone and THN are presented in Figs. 16,17 [14]. The selected ligands satisfy Lipinski’s rule of five as log p < 5, molecular weight < 500 g/mol, number of hydrogen bond acceptors < 10, number of hydrogen bond donors < 5 and number of rotatable bonds < 10.

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