PHARMACOPHORE DISTANCE MAPPING AND DOCKING STUDY OF SOME BENZIMIDAZOLE ANALOGS AS A2A RECEPTOR ANTAGONISTS
Abstract
Extracellular adenosine regulates a wide range of functions in higher organisms, in which the effects are mediated by a family of four class A (rhodopsin-like) GPCRs, a, adenosine receptors known as A1, A2A, A2B, and A3. A2A antagonists, either alone or in combination with dopamine agonists, can have a role in the treatment of neurodegenerative movement disorders such as Parkinson’s disease and Huntington’s disease. The concept of a pharmacophore is widely used in modern drug design and it is generally defined as the 3D arrangement of certain features in the ligand that are responsible for its activity against a particular protein target. Docking involves, the process of fitting the ligand into receptor, and the compounds which fit in them properly are assumed to be active for that receptor and it gives corresponding docking scores.
Keywords:
Pharmacophore, Docking, Adenosine Receptor, Parkinson's disease, Huntington's diseaseDOI
https://doi.org/10.25004/IJPSDR.2010.020116References
2. Paul Leff. Drugs and Pharmaceutical Sciences: Receptor- Based Drug Design. 1999, 89:323-330.
3. Williams M, Glennon R, Pieter BM. Receptor Pharmacology and Function, 1989, 18: 1-10.
4. Patrizia Minetti. 2-n-Butyl-9-methyl-8-[1, 2, 3] triazol-2-yl-9H-purin-6-ylamine and analogues as A2A Adenosine receptor antagonists: Design, Synthesis and Pharmacological Characterization. J. Med. Chem. 2005; 4: 6887-6896.
5. Douglas P, Ivan Diamond, Adrienne S. Gordon. The role of the neuromodulator adenosine in alcohol’s actions: Neurotransmitter Review 1997; 21(2): 136-137.
6. Latini S, Pedata F.Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J. Neurochem. 2001; 79(3):463-484.
7. Jacobson KA, Van Galen PJM, Williams M. Adenosine Receptors J. Med. Chem. 1992; 35: 407-422.
8. Micaela Morelli et al. Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications: Neurotransmitter Review 2007; 225.
9. Xiaohu Zhang et al. Lead Optimization of 4-Acetylamino-2-(3, 5- dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A Adenosine Receptor antagonists for the treatment of Parkinson’s disease. J. Med. Chem. 2008; 51(22): 7099-7110.
10. Anthony HV, Schapira et al. Novel pharmacological targets for the treatment of Parkinson’s disease: Nature’s Reviews, 2008; 5: 845-854.
11. Mc Grath J. Protect; Restore; Replace; Stimulate: Parkinson’s disease in 2020. Parkinsonism related disorder 2008; 12.
12. Emilia Mabel Gatto. Neuroprotection in Parkinson’s Disease- A Commentary. Neurotoxicity Research 2002; 4(2):141-145.
13. Anthony HV, Schapira et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nature’s reviews/ Drug discover 2006; 5: 845-850.
14. Ettore Novellino et al. 2-(Benzimidazol-2-yl) quinoxalines: A novel class of selective antagonists at human A1 and A3 adenosine receptors designed by 3D database searching. J. Med. Chem. 2005; 48 (26): 8253-8260.
15. Abraham DJ, Burger’s Medicinal Chemistry and Drug Discover., 6th ed, Drug Discovery, Jhon Wiley and Sons Inc. 2003, 1, 253.
16. Glide 4.5 User Manual, Schrodinger Press, 5.
17. www.rcsb.org/3eml_pdb.htm.
18. Jaakola VP, The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist. Science 2008; 322: 1211-1215.
Published
Abstract Display: 229 
PDF Downloads: 343 
