Imidazoline-1 receptor ligands as apoptotic agents: Pharmacophore modeling and virtual docking study

Combinatorial Chemistry and High Throughput Screening

Volumn 16, Issue 4, 2013, Pages 298-319

  Nikolic, Katarina ^a   Veljkovic, Nevena ^b   Gemovic, Branislava ^b   Srdic Rajic, Tatjana ^c   Agbaba, Danica ^a  

^a UNIVERSITY OF BELGRADE   (Serbia)

^b UNIVERSITY OF BELGRADE   (Serbia)

^c INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA   (Serbia)

Author keywords

Apoptotic activity; I1 imidazoline receptor; I1 IR agonist; I1 IR antagonist; Pharmacophore modeling; Structure activity relationship; Virtual docking

Indexed keywords

ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT; ANTINEOPLASTIC AGENT; ARGININE; EFAROXAN; GLUTAMIC ACID; IMIDAZOLINE 1 RECEPTOR; IMIDAZOLINE 1 RECEPTOR AGONIST; IMIDAZOLINE 1 RECEPTOR ANTAGONIST; IMIDAZOLINE RECEPTOR; MOXONIDINE; NISCHARIN; PROTEIN; RILMENIDINE; UNCLASSIFIED DRUG; VALINE;

ANIMAL CELL; APOPTOSIS; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER CELL CULTURE; CELL STRAIN K 562; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVITY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; HUMAN; HUMAN CELL; LIGAND BINDING; MOLECULAR DOCKING; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RAT; REGRESSION ANALYSIS; SPECTROSCOPY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BENZOFURANS; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; IMIDAZOLES; IMIDAZOLINE RECEPTORS; K562 CELLS; LIGANDS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; OXAZOLES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 84877962730     PISSN: 13862073     EISSN: 18755402     Source Type: Journal    
DOI: 10.2174/1386207311316040004     Document Type: Article

References (75)

1. Bousquet, P.; Feldman, J.; Schwartz, J. Central cardiovascular effects of alpha adrenergic drugs: Differences between catecholamines and imidazolines. J. Pharmacol. Exp. Ther., 1984, 230, 232-236.
2. Ernsberger, P.; Meeley, M.P.; Mann, J.J.; Reis, D.J. Clonidine binds to imidazole binding sites as well as α(2)-adrenoceptors in the ventrolateral medulla. Eur. J. Pharmacol., 1987, 134, 1-13.
3. Halaris, A.; Piletz, J.E. Relevance of imidazoline receptors and agmatine to psychiatry: a decade of progress. Ann. NY Acad. Sci., 2003, 1009, 1-20.
4. Morgan, N.G.; Chan, S.L. Imidazoline binding sites in the endocrine pancreas: can they fulfil their potential as targets for the development of new insulin secretagogues? Curr. Pharm. Des., 2001, 7, 1413-1431.
5. 2-adrenoceptor states plus a nonadrenergic site on human platelet plasma membranes. Biochem. Pharmacol., 1991, 42, 569-584.
6. Heemskerk, F.M.; Dontenwill, M.; Greney, H.; Vonthron, C.; Bousquet, P. Evidence for the existence of imidazoline-specific binding sites in synaptosomal plasma membranes of the bovine brainstem. J. Neurochem., 1998, 71, 2193-2202.
7. Ernsberger, P.; Shen, I.H. Membrane localization and guanine nucleotide sensitivity of medullary I1 imidazoline binding sites. Neurochem. Int., 1997, 30, 17-23.
8. 2-adrenoceptors. Ann. N.Y. Acad. Sci., 1999, 881, 123-135.
9. 3H] clonidine to I1-imidazoline sites in bovine adrenal medullary membranes. Naunyn-Schmiedeberg's Arch. Pharmacol., 1993, 348, 70-76.
10. Ernsberger, P.; Piletz, J.E.; Graff, L.M.; Graves, M.E. Optimization of radioligand binding assays for I1-imidazoline sites. Ann. N.Y. Acad. Sci., 1995, 763, 163-168.
11. Separovic, D.; Kester, M.; Ernsberger, P. Coupling of I1- imidazoline receptors to diacylglyceride accumulation in PC12 rat pheochromocytoma cells. Mol. Pharmacol., 1996, 49, 668-675.
12. Piletz, J.E.; Sletten, K. Nonadrenergic imidazoline binding sites on human platelets. J. Pharmacol. Exp. Ther., 1993, 267, 1493-1502.
13. Felsen, D.; Ernsberger, P.; Sutaria, P.M.; Nejat, R.J.; Nguyen, P.; May, M.; Breslin, D. S.; Marion, D. N.; Vaughan, D. Jr. Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate. J. Pharmacol. Exp. Ther., 1994, 268, 1063-1071.
14. Dupuy, L.; Urosevic, D.; Greney, H.; Quaglia, W.; Pigini, M.; Brasili, L.; Dontenwill, M.; Bousquet, P. I1 imidazoline receptormediated effects on apoptotic processes in PC12 cells. Cell Death Differentiation, 2004, 11, 1049-1052.
15. Zhang, J.; El Mas, M.M.; Abdel-Rahman, A.A. Imidazoline I(1) receptor-induced activation of phosphatidylcholine-specific phospholipase C elicits mitogen-activated protein kinase phosphorylation in PC12 cells. Eur. J. Pharmacol., 2001, 415, 117- 125.
16. Greney, H.; Ronde, P.; Magnier, C.; Maranca, F.; Rascente, C.; Quaglia, W.; Giannella, M.; Pigini, M.; Brasili, L.; Lugnier, C.; Bousquet, P.; Dontenwill, M. Coupling of I1-imidazoline receptors to the cAMP pathway: studies with a highly selective ligand, benazoline. Mol. Pharm., 2000, 57, 1142-1151.
17. Zhang, J.; Abdel-Rahman, A.A. Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (I1)-receptor-mediated hypotension. J. Pharmacol. Exp. Ther., 2005, 314, 945-952.
18. Edwards, L.; Fishman, D.; Horowitz, P.; Bourbon, N.; Kester, M.; Ernsberger, P. The I(1)-imidazoline receptor in PC12 pheochromocytoma cells activates protein kinases C, extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK). J. Neurochem., 2001, 79, 931-940.
19. Edwards, L.; Ernsberger, P. The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase. Brain. Res., 2003, 980, 71-79.
20. Ernsberger, P. The I(1)-imidazoline receptor and its cellular signaling pathways. Ann. N.Y. Acad. Sci., 1999, 881, 35-53.
21. Evinger, M.J.; Ernsberger, P.; Regunathan, S.; Reis, D.J, Regulation of phenylethanolamine N-methyltransferase gene expression by imidazoline receptors in adrenal chromaffin cells. J. Neurochem., 1995, 65, 988-997.
22. Nicolotti, O.; Carotti, A.; Carrieri, A.; Pigini, M.; Gentili, F.; Brasili, L.; Giannella, M.; Quaglia, W.; Piergentili, A.; Bousquet, P.; Dontenwill, M Pharmacophore development and 3D-QSAR study of I1 imidazoline binding site ligands. Med. Chem. Res., 2004, 13, 170-189.
23. Schann, S.; Greney, H.; Gasparik, V.; Dontenwill, M.; Rascente, C.; Lacroix, G.; Monassier, L.; Bruban, V.; Feldman, J.; Ehrhardt, J.-D.; Bousquet, P. Methylation of imidazoline related compounds leads to loss of α2-adrenoceptor affinity. Synthesis and biological evaluation of selective I 1 imidazoline receptor ligands. Bioorg. Med. Chem., 2012, 20, 4710-4715.
24. Bruban, V.; Feldman, J.; Greney, H. et al. Respective contributions of α-adrenergic and non-adrenergic mechanisms in the hypotensive effect of imidazoline-like drugs. Br. J. Pharmacol., 2001, 133, 261- 266.
25. Schann, S.; Bruban, V.; Pompermayer, K.; Feldman, J.; Pfeiffer, B.; Renard, P.; Scalbert, E.; Bousquet, P.; Ehrhardt, J.D. Synthesis and biological evaluation of pyrrolinic isosteres of rilmenidine. Discovery of cis-/trans-dicyclopropylmethyl-(4, 5-dimethyl-4, 5- dihydro-3H-pyrrol-2-yl)- amine (LNP 509): an I 1 imidazoline receptor selective ligand with hypotensive activity. J. Med. Chem., 2001, 44, 1588 -1593.
26. Urosevic, D.; Schann, S.; Ehrhardt, J.D.; Bousquet, P.; Greney, H. LNP 906, the first high-affinity photoaffinity ligand selective for I 1 imidazoline receptors. Br. J. Pharmacol., 2004, 142, 609-617.
27. Greney, H.; Urosevic, D.; Schann, S.; Dupuy, L.; Bruban, V.; Ehrhardt, J.D.; Bousquet, P.; Dontenwill, M. [125I]2-(2-chloro-4- iodo-phenylamino)-5- methyl-pyrroline (LNP 911), a high-affinity radioligand selective for I1 imidazoline receptors. Mol. Pharmacology, 2002, 62, 181-191.
28. Piletz, J.E.; Ivanov, T.R.; Sharp, J.D et al. Imidazoline receptor antisera-selected (IRAS) cDNA: Cloning and characterization. DNA Cell Biol., 2000, 19, 319-329.
29. Dontenwill, M.; Piletz, JE.; Chen, M.; Baldwin, J.; Pascal, G.; Ronde, P.; Dupuy, L.; Greney, H.; Takeda, K.; Bousquet, P. IRAS is an anti-apoptotic protein. Ann. N.Y. Acad. Sci., 2003, 1009, 400- 412.
30. Alahari, S.K.; Lee, J.W.; Juliano, R.L. Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration. J. Cell. Biol., 2000, 151, 1141-1154.
31. Piletz, J.E.; Jones, J.C.; Zhu, H.; Bishara, O.; Ernsberger, P. Imidazoline receptor antisera-selected cDNA clone and mRNA distribution. Ann. N.Y. Acad. Sci., 1999, 881, 1-7.
32. Piletz, J.E.; Wang, G.; Zhu, H. Cell signaling by imidazoline-1 receptor candidate, IRAS, and the nischarin homologue. Ann. N.Y. Acad. Sci., 2003b, 1009, 392-399.
33. Li, F.; Wu, N.; Su, R.B.; Zheng, J.Q.; Xu, B.; Lu, X.Q.; Cong, B.; Li, J. Involvement of Phosphatidylcholine-Selective Phospholipase C in Activation of Mitogen-Activated Protein Kinase Pathways in Imidazoline Receptor Antisera-Selected Protein. J. Cell. Biochem., 2006, 98, 1615-1628.
34. Zhang, J.; Abdel-Rahman, A.A. Nischarin as a functional imidazoline (I1) receptor. FEBS Letters, 2006, 580, 3070-3074.
35. Sun, Z.; Chang, C.H.; Ernsberger, P. Identification of IRAS/Nischarin as an I1-imidazoline receptor in PC12 rat pheochromocytoma cells. J. Neurochem., 2007, 101, 99-108.
36. Xu, Y.; Seet, L.F.; Hanson, B.; Hong, W. The Phox homology (PX) domain, a new player in phosphoinositide signaling. Biochem. J., 2001, 360, 513-530.
37. Alahari, S.K. Nischarin inhibits Rac induced migration and invasion of epithelial cells by affecting signaling cascades involving PAK. Exp. Cell. Res., 2003, 288, 415-424.
38. Baranwal, S.; Wang, Y.; Rathinam, R.; Lee, J.; Jin, L.; McGoey, R.; Pylayeva, Y.; Giancotti, F.; Blobe, G.C.; Alahari, S.K. (2011) Molecular Characterization of the Tumor-Suppressive Function of Nischarin in Breast Cancer. J. Natl. Cancer. Inst., 2011, 103, 1513- 1528.
39. Gentili, F.; Bousquet, P.; Brasili, L. et al. Imidazoline Binding Sites (IBS) Profile Modulation: Key Role of the Bridge in Determining I1-IBS or I2-IBS Selectivity within a Series of 2- Phenoxymethylimidazoline Analogues. J. Med. Chem., 2003, 46, 2169-2176.
40. Becke, A.D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys., 1993, 98, 5648-5652.
41. Lee, C.; Yang, W.; Parr, R.G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev., 1988, B37, 785-789.
42. Gaussian 98 (Revision A.7) Frisch MJ et al. Gaussian, Inc., 1998, Pittsburgh PA.
43. Remko, M.; Walshb, O.A.; Richardsb, W.G. Molecular structure and gas-phase reactivity of clonidine andrilmenidine: Two-layered ONIOM calculations. Phys. Chem. Chem. Phys., 2001, 3, 901-907.
44. Remko, M.; Van Duijnen, P.T.; Swart, M. Theoretical study of molecular structure, tautomerism, and geometrical isomerism of Nmethyl and N-phenyl substituted cyclic imidazolines, oxazolines and thiazolines. Struct. Chem., 2003, 14, 271-278.
45. Remko, M.; Swart, M.; Bickelhaupt, M. Theoretical Study of Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of some Centrally Acting Antihypertensives. Bioorg. Med. Chem., 2006, 14, 1715-1728.
46. Nikolic, K.; Filipic, S.; Agbaba, D. QSAR study of imidazoline antihypertensive drugs. Bioorg. Med. Chem., 2008, 16, 7134-7140.
47. Nikolic, K.; Filipic, S.; Agbaba, D. QSAR study of selective I1- imidazoline receptor ligands. SAR QSAR Environ. Res., 2008, 20, 133-144.
48. ChemAxon MarvinSketch 5.5.1.0 program, Budapest, Hungary, 2011. www.chemaxon.com/products.html.
49. Pentacle, Version 1.0.6.; Molecular Discovery Ltd, Perugia, Italy, 2009. http://www.moldiscovery.com/soft-pentacle.php.
50. Pastor, M.; Cruciani, G.; McLay, I.; Pickett, S.; Clementi, S. GRid- INdependent. Descriptors (GRIND): A novel class of alignmentindependent three-dimensional molecular descriptors. J. Med. Chem., 2000, 43, 3233-3243.
51. Eriksson, L.; Johansson, E.; Kettaneh-Wold, N.; Trygg, J.; Wikstrom, C.; Wold, S (Eds.) Multi-and Megavariate Data Analysis. Basic Principles and Applications I, 2nd ed, Umetrics Academy, Umeå, 2001.
52. Allen, D.M. The relationship between variable selection and data augmentation and a method for prediction. Technometrics, 1974, 16, 125-127.
53. Wold, S.; Johansson, E.; Cocchi, M. 3D-QSAR in drug design, theory, methods, and applications. H. Kubinyi Ed., ESCOM Science Publishers: Leiden, 1993, pp 523-550.
54. Karplus, K. SAM-T08: HMM-based Protein Structure Prediction. Nucleic Acids Research, 2009, 37(S2), W492-W497.
55. Katzman, S.; Barrett, C.; Thiltgen, G.; Karchin, R.; Karplus, K. Predict-2nd: a tool for generalized protein local structure prediction. Bioinformatics, 2008, 24, 2453-2459.
56. Shackelford, G.; Karplus, K. Contact Prediction using Mutual Information and Neural Nets. Proteins: Structure, Function and Bioinformatics, 2007, 69(S8), 159-164.
57. Karplus, K.; Katzman, S.; Shackleford, G.; Koeva, M.; Draper, J.; Barnes, B.; Soriano, M.; Hughey, R. SAM-T04: what's new in protein-structure prediction for CASP6. Proteins: Structure, Function and Bioinformatics, 2005, 61(S7), 135-142.
58. Schrödinger Suite 2011 Protein Preparation Wizard, Epik version 2.2, Schrödinger, LLC, New York, NY, 2011.
59. Impact version 5.7, Schrödinger, LLC, New York, NY, 2011.
60. Prime version 3.0, Schrödinger, LLC, New York, NY, 2011.
61. Maestro version 9.2, Schrödinger, LLC, New York, NY, 2011.
62. Macro Model, version 9.9, Schrödinger, LLC, New York, NY, 2011.
63. Veljkovic, V.; Veljkovic, N.; Esté, J.A.; Hüther, A.; Dietrich, U. Application of the EIIP/ISM bioinformatics concept in development of new drugs. Curr. Med. Chem., 2007, 14, 441-453.
64. Open Eye Scientific Software, FRED Receptor, Version 2.2.5, Inc. 9 Bisbee Ct, Suite D, Santa Fe, New Mexico 87508. March 17, 2009. www.eyesopen.com.
65. McGann, M. FRED Pose Prediction and Virtual Screening Accuracy. J. Chem. Inf. Model., 2011, 51, 578-596.
66. Eldridge, M.D.; Murray, C.W.; Auton, T.R.; Paolini, G.V.; Mee, R.P. Empirical scoring functions. I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J. Comput.-Aided Mol. Des., 1997, 11, 425- 445.
67. Piletz, J.E.; Zhu, H.; Chikkala, D.N. Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J. Pharmacol. Exp. Ther., 1996, 279, 694-702.
68. Byre, G.; Mostad, A.; Rømming, C. Crystal and molecular structure of clonidine hydrochloride, 2-(2, 6 dichlorophenylamino)- 2-imidazoline hydrochloride. Acta Chem. Scand., 1976, B30, 843- 846.
69. Veljkovic, N.; Glisic, S.; Prljic, J.; Perovic, V.; Botta, M.; Veljkovic, V. Discovery of new therapeutic targets by the informational spectrum method. Curr. Protein Pept. Sci., 2008, 9, 493-506.
70. Mancini, M.; Veljkovic, N. et al. 14-3-3 ligand prevents nuclear import of c-ABL protein in chronic myeloid leukemia. Traffic, 2009, 10, 637-647.
71. Veljkovic, V.; Niman, H.L.; Glisic, S.; Veljkovic, N.; Perovic, V.; Muller, C.P. Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor, BMC Structural Biology, 2009, 9, art no 62.
72. Tintori, C.; Veljkovic, N.; Veljkovic, V.; Botta, M. Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the Informational spectrum method. Proteins: Structure, Function and Bioformatics, 2010, 78, 3396-3408.
73. Ghemtio, L.; Pérez-Nueno, V.I.; Leroux, V.; Asses, Y.; Souchet, M.; Mavridis, L.; Maigret, B.; Ritchie, D.W. Recent trends and applications in 3D virtual screening. Combinatorial Chemistry and High Throughput Screening 2012, 15, 749-769.
74. Xiang, M.; Cao, Y.; Fan, W.; Chen, L.; Mo, Y. Computer-aided drug design: Lead discovery and optimization. Combinatorial Chemistry and High Throughput Screening, 2012, 15, 328-337.
75. Luu, T.T.T., Malcolm, N., Nadassy, K. Pharmacophore modeling methods in focused library selection-applications in the context of a new classification scheme. Combinatorial Chemistry and High Throughput Screening, 2011, 14, 488-499.