VIRTUAL SCREENING, PHARMACOPHORE MODELING, AND QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES ON HISTAMINE 4 RECEPTOR

Authors

  • SHOBANA S Department of Genetic Engineering, School of Bioengineering, SRM University, Kattankulathur, Kanchipuram - 603 203, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i12.19991

Keywords:

Histamine 4 receptor, Homology modeling, Docking, Pharmacophore modeling, Three-dimensional quantitative structure activity relationship

Abstract

 

 Objective: To find out novel inhibitors for histamine 4 receptor (H4R), the target for various allergic and inflammatory pathophysiological conditions.

Methods: Homology modeling of H4R was performed using easy modeler and validated using structure analysis and verification server, and with the modeled structure, virtual screening, pharmacophore modeling, and quantitative structure activity relationship (QSAR) studies were performed using the Schrodinger 9.3 software.

Results: Among all the synthetic and natural ligands, hesperidin, vitexin, and diosmin were found to have the highest dock score, and with that, a five-point pharmacophore model was developed consisting of two hydrogen bond acceptor and three ring atoms, and the pharmacophore hypothesis yielded a statistically significant three-dimensional QSAR (3D-QSAR) model with a correlation coefficient of r2=0.8962 as well as good predictive power.

Conclusion: The pharmacophore-based 3D-QSAR model generated from natural antihistamines can provide intricate structural knowledge about a new class of anti-allergic and anti-inflammatory drug research.

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Author Biography

SHOBANA S, Department of Genetic Engineering, School of Bioengineering, SRM University, Kattankulathur, Kanchipuram - 603 203, Tamil Nadu, India.

Assistant Professor(Sr.G)

Department of Genetic Engineering

SRM University.

References

Parsons ME, Ganellin CR. Histamine and its receptors. Br J Pharmacol 2006;147 Suppl 1:S127-35.

Akdis CA, Simons FE. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006;533(1-3):69-76.

Hong ST, Bang S, Paik D, Kang J, Hwang S, Jeon K, et al. Histamine and its receptors modulate temperature-preference behaviors in Drosophila. J Neurosci 2006;26(27):7245-56.

Sander LE, Lorentz A, Sellge G, Coëffier M, Neipp M, Veres T, et al. Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Gut 2006;55(4):498-504.

Szukiewicz D, Szewczyk G, Klimkiewicz J, Pyzlak M, Maslinska D. The role of histamine and its receptors in the development of ovarian follicles in vitro. Inflamm Res 2006;55 Suppl 1:S49-50.

Breunig E, Michel K, Zeller F, Seidl S, Weyhern CW, Schemann M. Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. J Physiol 2007;583:731-42.

Zampeli E, Tiligada E. The role of histamine H4 receptor in immune and inflammatory disorders. Br J Pharmacol 2009;157(1):24-33.

Li YY, Hou TJ, Goddard WA 3rd. Computational modeling of structure-function of g protein-coupled receptors with applications for drug design. Curr Med Chem 2010;17(12):1167-80.

Li Y, Hou T. Computational simulation of drug delivery at molecular level. Curr Med Chem 2010;17(36):4482-91.

Goddard WA 3rd, Kim SK, Li Y, Trzaskowski B, Griffith AR, Abrol R. Predicted 3D structures for adenosine receptors bound to ligands: Comparison to the crystal structure. J Struct Biol 2010;170(1):10-20.

Kim SK, Li Y, Abrol R, Heo J, Goddard WA 3rd. Predicted structures and dynamics for agonists and antagonists bound to serotonin 5-HT2B and 5-HT2C receptors. J Chem Inf Model 2011;51(2):420-33.

Li Y, Zhu F, Vaidehi N, Goddard WA 3rd, Sheinerman F, Reiling S, et al. Prediction of the 3D structure and dynamics of human DP G-protein coupled receptor bound to an agonist and an antagonist. J Am Chem Soc 2007;129(35):10720-31. 13. Kim SK, Li Y, Park C, Abrol R, Goddard WA 3rd. Prediction of the three-dimensional structure for the rat urotensin II receptor, and comparison of the antagonist binding sites and binding selectivity between human and rat receptors from atomistic simulations. Chem Med Chem 2010;5(9):1594-608.

Kottke T, Sander K, Weizel L, Schneider EH, Seifert R, Stark H. Receptor-specific functional efficacies of alkyl imidazoles as dual histamine H3/H4 receptor ligands. Eur J Pharmacol 2011;654(3):200-8.

Cowart MD, Altenbach RJ, Liu H, Hsieh GC, Drizin I, Milicic I, et al. Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: A new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models. J Med Chem 2008;51(20):6547-57.

Smits RA, Adami M, Istyastono EP, Zuiderveld OP, van Dam CM, de Kanter FJ, et al. Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists. J Med Chem 2010;53(6):2390-400.

Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, et al. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther 2004;309(1):404-13.

Terzioglu N, van Rijn RM, Bakker RA, De Esch IJ, Leurs R. Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists. Bioorg Med Chem Lett 2004;14(21):5251-6.

Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature 2011;475(7354):65-70.

Zhang M, Thurmond RL, Dunford PJ. The histamine H(4) receptor: A novel modulator of inflammatory and immune disorders. Pharmacol Ther 2007;113(3):594-606.

Vijayasri S, Hopper W. Towards the identification of novel phytochemical leads as macrodomain inhibitors of chikungunya virus using molecular docking approach. J Appl Pharm Sci 2017;4:74-82.

Walter M, Kottke T, Stark H. The histamine H4 receptor: Targeting inflammatory disorders. Eur J Pharmacol 2011;668(1-2):1-5.

Kiss R, Noszál B, Rácz A, Falus A, Eros D, Keseru GM. Binding mode analysis and enrichment studies on homology models of the human histamine H4 receptor. Eur J Med Chem 2008;43(5):1059-70.

Feng Z, Hou T, Li Y. Docking and MD study of histamine H4R based on the crystal structure of H1R. J Mol Graph Model 2013;39:1-12.

Kiss R, Kovári Z, Keseru GM. Homology modelling and binding site mapping of the human histamine H1 receptor. Eur J Med Chem 2004;39(11):959-67.

Banerjee S, Sen D. Pharmacophore based atomic QSAR study of novel quinaxaline 1, 4-di-N-oxides as selective non-cytotoxic anti-tubercular agents. Int J Chem Stud 2013;1:110-7.

Ugale VG, Patel HM, Surana SJ. Molecular modeling studies of quinoline derivatives as VEGFR-2 tyrosine kinase inhibitors using pharmacophore based 3D QSAR and docking approach. Arab J Chem 2017;10:S1980-2003.

Devi B, Rajagopala K, Elizabeth E. Pharmacophoric screening of various edophytic fungal metabolites. Asian J Pharm Clin Res 2017;10:140-6.

Devi SK, Velmurugan D. Molecular modelling, QSAR and pharmacophore studies on anti-viral, anti-malarial and anti-inflammatory bioactive compounds from marine sources. Asian J Pharm Clin Res 2015;8:3.

Dharani RS, Ranjitha R, Sripathi R, Muhammad KA, Ravi S. Docking studies in target proteins involved in antibacterial action mechanisms: Alkaloids isolated from Scutellaria genus. Asian J Pharm Clin Res 2016;9:5.

Al-Jomaily M, Arafat T, Al-Kaissi E, Ghattas MA, Muhi-Eldeen Z. Synthesis of amino acetylenic benzophenone derivatives as H3-antagonists. Int J Pharm Pharm Sci 2015;7:6.

Kaur G, Singh R. Thiadiazole analogs as potential pharmacological agents: A brief review. Int J Pharm Pharm Sci 2014;6:8.

Published

01-12-2017

How to Cite

S, S. “VIRTUAL SCREENING, PHARMACOPHORE MODELING, AND QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES ON HISTAMINE 4 RECEPTOR”. Asian Journal of Pharmaceutical and Clinical Research, vol. 10, no. 12, Dec. 2017, pp. 150-4, doi:10.22159/ajpcr.2017.v10i12.19991.

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