17Jun 2019

IN SILICO MOLECULAR DOCKING AND ADME/T STUDIES OF SELECTED COMPOUNDS OF SWERTIA CHIRATA (GENTIANACEAE) AGAINST TWO RECEPTORS OF TYPE 2 DIABETES.

  • Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh.
  • Department of Pharmacy,Atish Dipankar University of Science and Technology, Dhaka-1230, Bangladesh.
  • Drug Discovery, GUSTO A Research Group, Chittagong, Bangladesh.
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Background: Diabetes is a metabolic disorder that leads to more complex diseases if kept untreated for a long time. Current oral hypoglycemic drugs are managing diabetes to a satisfactory level although some are associated with intense side effects. Historically natural products are playing the vital role for providing ideal lead molecules for drug development. In silico methods are ahead of conventional drug development methods for screening compounds against a target receptor with higher success rates. Thus this study aims at finding novel compounds from Swertia chirata that can be effectively used against diabetes through computational methods. Material and Methods: The compounds of S. chirata were computationally screened by docking with Pancreatic alpha amylase (PDB ID: 1PPI) and Fructose-1,6-bisphosphatase (PDB ID: 2JJK) by Maestro v10.1 of Schrodinger LLC. In addition, ADME/T properties were analyzed through SwissADME. Best docked poses were analyzed and visualized using Discovery studio software. Results: Molecular docking studies revealed that among the compounds of S. chirata, Swertiamarin had the highest docking score of -6.803 against 1PPI and Sweroside had the highest docking score of -5.161 against 2JJK, ensuring strong receptor-ligand binding. Also ADME/T analysis showed that these two molecules possess suitable properties to be considered as drug candidates. Conclusion: The molecular docking, binding patterns and ADME/T properties of compounds in this study confirms that these phytochemicals can be good lead molecules in the treatment of diabetes.

  1. Aicher, T. D., Boyd, S. A., McVean, M., & Celeste, A. (2010). Novel therapeutics and targets for the treatment of diabetes. Expert Review of Clinical Pharmacology, 3(2), 209?229. https://doi.org/10.1586/ecp.10.1
  2. Balasundari, P., Singh, S. K., & Kavimani, S. (2005). Free radical scavenging of xanthones from Swertia chirata Buchham and tumor cell growth inhibition. Main Group Chemistry, 4(3), 177?185. https://doi.org/10.1080/10241220500324209
  3. Bhattacharya, S. K., Reddy, P. K. S. P., Ghosal, S., Singh, A. K., & Sharma, P. V. (1976). Chemical constituents of gentianaceae XIX: CNS-depressant effects of swertiamarin. Journal of Pharmaceutical Sciences, 65(10), 1547?1549. https://doi.org/10.1002/jps.2600651037
  4. BIOVIA, D. S. (2017). Discovery Studio Visualizer. San Diego, CA, USA.
  5. Boulton, A. J. M., Vinik, A. I., Arezzo, J. C., Bril, V., Feldman, E. L., Freeman, R., ? Ziegler, D. (2005). Diabetic Neuropathies: A statement by the American Diabetes Association. Diabetes Care, 28(4), 956?962. https://doi.org/10.2337/diacare.28.4.956
  6. Chakravarty, A. K., Mukhopadhyay, S., & Das, B. (1991). Swertane triterpenoids from Swertia chirata. Phytochemistry, 30(12), 4087?4092.
  7. Chandrasekar, B., Bajpai, M. B., & Mukherjee, S. K. (1990). Hypoglycemic activity of Swertia chirayita (Roxb ex Flem) Karst. Indian Journal of Experimental Biology, 28(7), 616?618.
  8. Daina, A., Michielin, O., & Zoete, V. (2014). iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach. Journal of Chemical Information and Modeling, 54(12), 3284?3301. https://doi.org/10.1021/ci500467k
  9. Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
  10. Duffy, F. J., Devocelle, M., & Shields, D. C. (2015). Computational Approaches to Developing Short Cyclic Peptide Modulators of Protein?Protein Interactions. In P. Zhou & J. Huang (Eds.), Computational Peptidology (pp. 241?271). https://doi.org/10.1007/978-1-4939-2285-7_11
  11. Erion, M. D., Poelje, P. D. van, Dang, Q., Kasibhatla, S. R., Potter, S. C., Reddy, M. R., ? Lipscomb, W. N. (2005). MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proceedings of the National Academy of Sciences, 102(22), 7970?7975. https://doi.org/10.1073/pnas.0502983102
  12. Ertl, P., Rohde, B., & Selzer, P. (2000). Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties. Journal of Medicinal Chemistry, 43(20), 3714?3717. https://doi.org/10.1021/jm000942e
  13. Fran?a, T. C. C., Guimar?es, A. P., Cortopassi, W. A., Oliveira, A. A., & Ramalho, T. C. (2013). Applications of docking and molecular dynamic studies on the search for new drugs against the biological warfare agents Bacillus anthracis and Yersinia pestis. Current Computer-Aided Drug Design, 9(4), 507?517. https://doi.org/10.2174/15734099113099990033
  14. Hay, M., Thomas, D. W., Craighead, J. L., Economides, C., & Rosenthal, J. (2014). Clinical development success rates for investigational drugs. Nature Biotechnology, 32, 40?51. https://doi.org/10.1038/nbt.2786
  15. Hebeisen, P., Kuhn, B., Kohler, P., Gubler, M., Huber, W., Kitas, E., ? Ruf, A. (2008). Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorganic & Medicinal Chemistry Letters, 18(16), 4708?4712. https://doi.org/10.1016/j.bmcl.2008.06.103
  16. Karan, M., Vasisht, K., & Handa, S. S. (1999). Antihepatotoxic activity of Swertia chirata on paracetamol and galactosamine induced hepatotoxicity in rats. Phytotherapy Research, 13(2), 95?101. https://doi.org/10.1002/(SICI)1099-1573(199903)13:2<95::AID-PTR379>3.0.CO;2-4
  17. Kawatkar, S., Wang, H., Czerminski, R., & Joseph-McCarthy, D. (2009). Virtual fragment screening: An exploration of various docking and scoring protocols for fragments using Glide. Journal of Computer-Aided Molecular Design, 23(8), 527?539. https://doi.org/10.1007/s10822-009-9281-4
  18. Li, G. Q., Kam, A., Wong, K. H., Zhou, X., Omar, E. A., Alqahtani, A., ? Chan, K. (2012). Herbal medicines for the management of diabetes. Advances in Experimental Medicine and Biology, 771, 396?413.
  19. Lionta, E., Spyrou, G., Vassilatis, D. K., & Cournia, Z. (2014). Structure-Based Virtual Screening for Drug Discovery: Principles, Applications and Recent Advances. Current Topics in Medicinal Chemistry, 14(16), 1923?1938. https://doi.org/10.2174/1568026614666140929124445
  20. Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1), 3?25. https://doi.org/10.1016/S0169-409X(96)00423-1
  21. Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221?234. https://doi.org/10.1007/s10822-013-9644-8
  22. Nickavar, B., & Abolhasani, L. (2013). Bioactivity-Guided Separation of an α-Amylase Inhibitor Flavonoid from Salvia virgata. Iranian Journal of Pharmaceutical Research : IJPR, 12(1), 57?61.
  23. Pickup, J. C., & Williams, G. (1991). Textbook of diabetes (Vol. 1). Wiley-Blackwell.
  24. Repasky, M. P., Murphy, R. B., Banks, J. L., Greenwood, J. R., Tubert-Brohman, I., Bhat, S., & Friesner, R. A. (2012). Docking performance of the glide program as evaluated on the Astex and DUD datasets: A complete set of glide SP results and selected results for a new scoring function integrating WaterMap and glide. Journal of Computer-Aided Molecular Design, 26(6), 787?799. https://doi.org/10.1007/s10822-012-9575-9
  25. Roglic, G., & World Health Organization (Eds.). (2016). Global report on diabetes. Geneva, Switzerland: World Health Organization.
  26. Saha, P., & Das, S. (2010). Highlighting the anti-carcinogenic potential of an ayurvedic medicinal plant, Swertia Chirata. Asian Pac J Cancer Prev, 11(6), 1445?1449.
  27. Shivaji, B., Tapas, K. S., Suvra, M., Prabhash, C. D., & Sridhar, S. (2000). Assessment of the anti-inflammatory effects of Swertia chirata in acute and chronic experimental models in male albino rats. Indian Journal of Pharmacology, 32(1), 21.
  28. Shivakumar, D., Williams, J., Wu, Y., Damm, W., Shelley, J., & Sherman, W. (2010). Prediction of Absolute Solvation Free Energies using Molecular Dynamics Free Energy Perturbation and the OPLS Force Field. Journal of Chemical Theory and Computation, 6(5), 1509?1519. https://doi.org/10.1021/ct900587b
  29. Suryawanshi, S., Mehrotra, N., Asthana, R. K., & Gupta, R. C. (2006). Liquid chromatography/tandem mass spectrometric study and analysis of xanthone and secoiridoid glycoside composition of Swertia chirata, a potent antidiabetic. Rapid Communications in Mass Spectrometry, 20(24), 3761?3768. https://doi.org/10.1002/rcm.2795
  30. Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002). Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. Journal of Medicinal Chemistry, 45(12), 2615?2623. https://doi.org/10.1021/jm020017n
  31. Woodrow, P. (2011). Intensive Care Nursing : A Framework for Practice. https://doi.org/10.4324/9780203808122
  32. Yadav, R., Bhartiya, J. P., Verma, S. K., & Nandkeoliar, M. K. (2013). The Evaluation of Serum Amylase in the Patients of Type 2 Diabetes Mellitus, with a Possible Correlation with the Pancreatic Functions. Journal of Clinical and Diagnostic Research : JCDR, 7(7), 1291?1294. https://doi.org/10.7860/JCDR/2013/6016.3120.

[Md. Nazmul Hasan, Arkajyoti Paul, Ramiz Ahmed Sultan, Md. Tanveer Ahsan And Mohammed Kamrul Hossain. (2019); IN SILICO MOLECULAR DOCKING AND ADME/T STUDIES OF SELECTED COMPOUNDS OF SWERTIA CHIRATA (GENTIANACEAE) AGAINST TWO RECEPTORS OF TYPE 2 DIABETES. Int. J. of Adv. Res. 7 (Jun). 589-596] (ISSN 2320-5407). www.journalijar.com

Md. Nazmul Hasan
Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh

DOI:

Article DOI: 10.21474/IJAR01/9258      
DOI URL: https://dx.doi.org/10.21474/IJAR01/9258

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