PHARMACOPHORE ELUCIDATION AND DOCKING STUDIES ON ANTI-INFLAMMATORY COMPOUNDS OF MEDICINAL PLANTS FOR ULCERATIVE COLITIS

  • Hamsa N S Department of Biotechnology G.M Institute of Technology Davangere-06
  • Vandana P Nair Department of Biotechnology G.M Institute of Technology Davangere-06
  • Vivek Chandramohan Siddaganga institute of Techology Tumkur
  • Seema J Patel Department of Biotechnology G.M Institute of Technology Davangere-06

Abstract

ABSTRACT

Inflammatory bowel diseases such as Ulcerative Colitis (UC) are becoming common in this aging society throughout the world which includes formation of ulcers or open sores. Since, there is no known medical cure for UC; the therapeutic armamentarium is aimed at reducing the signs and symptoms associated with the disorder. The role of antibiotics in the treatment of severe active UC is controversialbecause the clinically used anti-inflammatory drugs suffer from the disadvantage of side effects and high cost of treatment. In the present study, NF-kB p50/p65 is docked in two different ways, one with the glucocorticoid receptor protein using ZDOCK in Accelrys Discovery Studio 3.5 and the other is screening and docking of400 anti-inflammatory natural compounds derived from plant source which offer a great hope in the identification of lead compounds.These compounds were investigated for their inhibitory activity by molecular docking studies and ADME/T properties of the compounds were analyzed for drug like candidates by using the commercial software's Accelrys Discovery Studio, Lead-IT and GOLD 5.1. Based on the docking results and toxicity analysis using TOPKAT, the best compounds determined are Ginkgetin, Bilobetin and Mesuaxanthone_B. The Pharmacophore studies have also shown that these compounds are having very less side effects and further investigations are requiredto take into clinical trials.

 

KEYWORDS: Inflammatory bowel disease, NF-kB p50/p65, Glucocorticoid, ZDOCK, TOPKAT

 

Author Biographies

Hamsa N S, Department of Biotechnology G.M Institute of Technology Davangere-06
Department of Biotechnology, M.Tech. in Bio-informatics
Vandana P Nair, Department of Biotechnology G.M Institute of Technology Davangere-06
Department of Biotechnology, M.Tech. in Bio-informatics
Vivek Chandramohan, Siddaganga institute of Techology Tumkur
Department of Biotechnology
Seema J Patel, Department of Biotechnology G.M Institute of Technology Davangere-06
Department of Biotechnology

References

REFERENCES

1. Lu SY, Jiang YJ, Lv J, Wu TX QS and Zhu WL: Molecular docking and molecular dynamics simulation studies of GPR40 receptor-agonist interactions. J Mol Graph Model 2010; 28: 766-774.

2. Rong Chen, Li Liand Zhiping Weng, ZDOCK: An Initial-Stage Protein Docking Algorithm. PROTEINS: Structure, Function and Genetics 2003; 52:80-87.

3. http://pubchem.ncbi.nlm.nih.gov/

4. www.Chemicalize.org

5. Lipinski CA, Franco I, Dominy BW, Feeney PJ: Experimental and computational approaches to estímate solubility and permeability in drug discovery and development settings. Advance Drug Delivery Review 1997; 23:3-25.

6. D Jayasimha Rayalu, D Muralidhara rao and D S Rao: Phytochemical screening and insilico approach for the identification of anti-stress compounds from medicinal plants. 2013; 4:324-334.

7. Daisy P, Suveena S: Solutions to pharmaceutical issues for anti-cancer drugs by accord excel. Asian journal of pharmaceutical and clinical research 2012; 5:149-158.

8. Rarey M, Kramer B, Lengauer T, Klebe G: A Fast Flexible Docking Method using an Incremental Construction Algorithm. Journal of Molecular Biology 1996; 261:470-489.

9. G Jones, P Wilett, R C Glen, A R Leach, R Taylor: Development and validation of a genetic algorithm for flexible docking. Journal of molecular Biology 1997; 267:727-748.

10. Vidyanath Chaudhary: Structure based inhibitor designing for Rac-alphaserine/threonine-proteinkinase in human. Journal of Advanced Bioinformatics Applications and Research 2012; 3:374-378.

11. Momany FA, Rone RJ. Validation of the general purpose QUANTA 3.2/CHARMm force field. Comp chem 1992; 13:888-900.

12. Van de Waterbeemd H, Gifford E. ADMET Insilico Modelling. Towards prediction Paradise? Nat Rev Drug Discovery 2003; 2:192-204.

13. CHS Venkataramana, KM Ramya Sravani, S Swetha Singh and V Madhavan. Insilico ADME and toxicity studies of some novel indole derivatives, Journal of Applied Pharmaceutical Science 2011; 1:159-162.

14. Wolber G, Kosara R, Pharmacophores from macromolecular complexes with Ligand Scout. In Pharmacophores and Pharmacophore Searches Edited by: Langer T, Hoffmann RD 2006; 32:131-150.

15. Wolber G, Seidel T, Bendix F, Langer T, Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discovery Today 2008; 13: 23-29.

16. Lavalle SM, Finn PW, Kavraki LE, Latombe J C, A Randomized Kinematics-Based Approach to Pharmacophore- Constrained Conformational Search and Database Screening. J Comput Chem 2000; 21:731-747.
Statistics
539 Views | 39 Downloads
How to Cite
N S, H., V. P. Nair, V. Chandramohan, and S. J. Patel. “PHARMACOPHORE ELUCIDATION AND DOCKING STUDIES ON ANTI-INFLAMMATORY COMPOUNDS OF MEDICINAL PLANTS FOR ULCERATIVE COLITIS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 6, no. 7, Aug. 2013, pp. 56-61, https://innovareacademics.in/journals/index.php/ajpcr/article/view/143.
Section
Articles