Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

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, Velmani (Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University) ;
  • AL Rashid, Mohammad Harun (Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University) ;
  • Majumder, Sayani (Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University) ;
  • Maiti, Partha Pratim (Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University) ;
  • Mandal, Subhash C (Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University)
  • Received : 2015.02.25
  • Accepted : 2015.05.13
  • Published : 2015.06.30
Download PDF
⟨ Previous Next ⟩

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 ($H_2O_2$), 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 $54{\times}55{\times}56$, 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.

Keywords

References

  1. Penney DP, Powers JM, Frank M, Willis C, Churukian C. Analysis and testing of biological stains - the biological stain commission procedures. Biotech Histochem. 2002;77(5-6):237-75. https://doi.org/10.1080/bih.77.5-6.237.275
  2. Singh M, Jindal SK, Kavia ZD, Jangid BL, Khem Chand. Traditional methods of cultivation and processing of henna. henna, cultivation, improvement and trade. India: Central Arid Zone Research Institute, Jodhpur. 2005. p. 21-4.
  3. The scientific committee on cosmetic products and non-food products intended for consumers [internet]. London: European Public Spaces; 2004. Available from: http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out254_en.pdf.
  4. Munday R, Smith BL, Fowke EA. Haemolytic activity and nephrotoxicity of 2-hydroxy-1,4-naphthoquinone in rats. J Appl Toxicol. 1991;11(2):85-90. https://doi.org/10.1002/jat.2550110203
  5. Kirkland D, Marzin D. An assessment of the genotoxicity of 2-hydroxy-1,4 naphthoquinone, the natural dye ingredient of henna. Mutat Res. 2003;537(2):183-99. https://doi.org/10.1016/S1383-5718(03)00077-9
  6. Biological macromolecular resource [internet]. USA: Protein data bank; 2014 [February 2014]. Available from: http://www.rcsb.org/pdb/home/home.do.
  7. Gupta D, Bleakley B, Gupta RK. Dragon's blood: botany, chemistry and therapeutic uses. J Ethnopharmacol. 2008;115(3):361-80. https://doi.org/10.1016/j.jep.2007.10.018
  8. Holstege CP, Mitchell K, Barlotta K, Furbee RB. Toxicity and drug interactions associated with herbal products: ephedra and St. John's Wort. Med Clin North Am. 2005;89(6):1225-57. https://doi.org/10.1016/j.mcna.2005.08.002
  9. Venkataramanan R, Komoroski B, Strom S. In vitro and in vivo assessment of herb drug interactions. Life Sci. 2006;78(18):2105-15. https://doi.org/10.1016/j.lfs.2005.12.021
  10. Jordan SA, Cunningham DG, Marles RJ. Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxic Appl Pharmacol. 2010;243(2):198-216. https://doi.org/10.1016/j.taap.2009.12.005
  11. Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, et al. Rapid pro-gressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet.1993;341(8842):387-91. https://doi.org/10.1016/0140-6736(93)92984-2
  12. Debelle FD, Nortier JL, De Prez EG, Garbar CH, Vienne AR, Salmon IJ, et al. Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol. 2002;13(2):431-6.
  13. Baliga MS, Jagetia GC, Ulloor JN, Baliga MP, Venkatesh P, Reddy R, et al. The evaluation of the acute toxicity and long term safety of hydroalcoholic extract of Sapthaparna (alstoniascholaris) in mice and rats. Toxicol Lett. 2004;151(2):317-26. https://doi.org/10.1016/j.toxlet.2004.01.015
  14. Calculation of molecular properties and bioactivity score [internet]. Slovak Republic: Molinspiration; 2014 [11 May 2014]. Available from: http://www.molinspiration.com/cgi-bin/properties.
  15. Souse SF, Fernandes PA, Ramos MJ. Protein-ligand docking: current status and future challenges. Proteins. 2006;65(1):15-26. https://doi.org/10.1002/prot.21082
  16. Hu X, Shelver WH. Docking studies of matrix metalloproteinase inhibitors: zinc parameters optimization to improve the binding free energy prediction. J Mol Graph Model. 2003;22(2):115-26. https://doi.org/10.1016/S1093-3263(03)00153-0
  17. Kubinyi H. Structure-based design of enzyme inhibitors and receptor ligands. Curr Opin Drug Discov Devel. 1998;1(1):4-15.
  18. Cadenas E. Basic mechanisms of antioxidant activity. Biofactors. 1997;6(4):391-7. https://doi.org/10.1002/biof.5520060404