Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl) amino)ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: In vivo activity indicates potential application in symptomatic and neuroprotective therapy for Parkinson's disease

Journal of Medicinal Chemistry

Volumn 53, Issue 5, 2010, Pages 2114-2125

  Ghoshs, Balaram ^a   Antonio, Tamara ^b   Reith, Maarten E A ^b   Dutta, Aloke K ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [4 [2 [(5 HYDROXY 1,2,3,4 TETRAHYDRONAPHTHALEN 2 YL)(PROPYL)AMINO]ETHYL]PIPERAZIN 1 YL]QUINOLIN 8 OL; 4 [4 [2 [(7 HYDROXY 1,2,3,4 TETRAHYDRONAPHTHALEN 2 YL)(PROPYL)AMINO]ETHYL]PIPERAZIN 1 YL]QUINOLIN 8 OL; DEOXYRIBOSE; DOPAMINE; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); QUINOLINE DERIVATIVE; RESERPINE; ROPINIROLE; SPIPERONE; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIOXIDANT ACTIVITY; ARTICLE; BINDING ASSAY; CATALEPSY; CELL DEATH; COMPLEX FORMATION; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; IN VITRO STUDY; IN VIVO STUDY; IRON CHELATION; LOCOMOTION; MALE; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; RAT;

ANIMALS; DISEASE MODELS, ANIMAL; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); HUMANS; IRON CHELATING AGENTS; LOCOMOTION; MAGNETIC RESONANCE SPECTROSCOPY; MALE; NEUROPROTECTIVE AGENTS; OXYQUINOLINE; PARKINSON DISEASE; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D3; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDRONAPHTHALENES;

EID: 77949421702     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901618d     Document Type: Article

References (42)

1. Wooten, G. F. Movement Disorders. Neurologic Principles and Practice; McGraw-Hill: New York, 1997; pp 153-160.
2. Paulus, W.; Jellinger, K. The neuropathology basis of different clinical subgroups of Parkinson's disease. J. Neuropathol. Exp. Neurol. 1991, 50, 743-755.
3. Mouradian, M. M. Recent advances in the genetics and pathogenesis of Parkinson disease. Neurology 2002, 58, 179-185.
4. Moore, D. J.; West, A. B.; Dawson, V. L.; Dawson, T. M. Molecular pathophysiology of Parkinson's disease. Annu. Rev. Neurosci. 2005, 28, 57-87.
5. Jenner, P. Oxidative stress in Parkinson's disease. Ann. Neurol. 2003, 53 (Suppl. 3), S26-S36; discussion S36-S38 .
6. Betarbet, R.; Sherer, T. B.; MacKenzie, G.; Garcia-Osuna, M.; Panov, A. V.; Greenamyre, J. T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 2000, 3, 1301-1306.
7. Dawson, T. M.; Dawson, V. L. Molecular pathways of neurodegeneration in Parkinson's disease. Science 2003, 302, 819-822.
8. Forno, L. S. Neuropathology of Parkinson's disease. J. Neuropathol. Exp. Neurol. 1996, 55, 259-272.
9. Spillantini, M. G.; Schmidt, M. L.; Lee, V. M.; Trojanowski, J. Q.; Jakes, R.; Goedert, M. alpha-synuclein in Lewy bodies. Nature 1997, 388, 839-840.
10. Berg, D.; Gerlach, M.; Youdim, M. B.; Double, K. L.; Zecca, L.; Riederer, P.; Becker, G. Brain iron pathways and their relevance to Parkinson's disease. J. Neurochem. 2001, 79, 225-236.
11. Jellinger, K. A. The role of ironin neurodegeneration: prospects for pharmacotherapy of Parkinson's disease. Drugs Aging 1999, 14, 115-140.
12. Wolozin, B.; Golts, N. Iron and Parkinson's disease. Neuroscientist 2002, 8, 22-32.
13. Faucheux, B. A.; Martin, M. E.; Beaumont, C.; Hunot, S.; Hauw, J. J.; Agid, Y.; Hirsch, E. C. Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson's disease. J. Neurochem. 2002, 83, 320-330.
14. Zecca, L.; Gallorini, M.; Schunemann, V.; Trautwein, A. X.; Gerlach, M.; Riederer, P.; Vezzoni, P.; Tampellini, D. Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes. J. Neurochem. 2001, 76, 1766-1773.
15. Ostrerova-Golts, N.; Petrucelli, L.; Hardy, J.; Lee, J. M.; Farer, M.; Wolozin, B. The A53T alpha-synuclein mutation increases irondependent aggregation and toxicity. J. Neurosci. 2000, 20, 6048-6054.
16. Turnbull, S.; Tabner, B. J.; El-Agnaf, O. M.; Moore, S.; Davies, Y.; Allsop, D. alpha-Synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. Free Radical Biol. Med. 2001, 30, 1163-1170.
17. Shamoto-Nagai, M.; Maruyama, W.; Yi, H.; Akao, Y.; Tribl, F.; Gerlach, M.; Osawa, T.; Riederer, P.; Naoi, M. Neuromelanin induces oxidative stress in mitochondria through release of iron: mechanism behind the inhibition of 26S proteasome. J. Neural Transm. 2006, 113, 633-644.
18. Zhang, X.; Xie, W.; Qu, S.; Pan, T.; Wang, X.; Le, W. Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration. Biochem. Biophys. Res. Commun. 2005, 333, 544-549.
19. Gaeta, A.; Hider, R. C. The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br. J. Pharmacol. 2005, 146, 1041-1059.
20. Goswami, A.; Dikshit, P.; Mishra, A.; Mulherkar, S.; Nukina, N.; Jana, N. R. Oxidative stress promotes mutant huntingtin aggregation and mutant huntingtin-dependent cell death by mimicking proteasomal malfunction. Biochem. Biophys. Res. Commun. 2006, 342, 184-190.
21. Kaur, D.; Andersen, J. K. Ironing out Parkinson's disease: is therapeutic treatment with iron chelators a real possibility? Aging Cell 2002, 1, 17-21.
22. Youdim, M. B.; Fridkin, M.; Zheng, H. Novel bifunctional drugs targeting monoamine oxidase inhibition and iron chelation as an approach to neuroprotection in Parkinson's disease and other neurodegenerative diseases. J. Neural Transm. 2004, 111, 1455-1471.
23. Zheng, H.; Weiner, L. M.; Bar-Am, O.; Epsztejn, S.; Cabantchik, Z. I.; Warshawsky, A.; Youdim, M. B.; Fridkin, M. Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Bioorg. Med. Chem. 2005, 13, 773-783.
24. Dutta, A. K.; Venkataraman, S. K.; Fei, X. S.; Kolhatkar, R.; Zhang, S.; Reith, M. E. Synthesis and biological characterization of novel hybrid 7-[[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino]-5,6,7,8-tetrahydro- naphthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors. Bioorg. Med. Chem. 2004, 12, 4361-4373.
25. Biswas, S.; Zhang, S.; Fernandez, F.; Ghosh, B.; Zhen, J.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Further structureactivity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}- 5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action. J. Med. Chem. 2008, 51, 101-117.
26. Biswas, S.; Hazeldine, S.; Ghosh, B.; Parrington, I.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Bioisosteric heterocyclic versions of 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen- 2-ol: identification of highly potent and selective agonists for dopamine D3 receptor with potent in vivo activity. J. Med. Chem. 2008, 51, 3005-3019.
27. Pierre, J. L.; Baret, P.; Serratrice, G. Hydroxyquinolines as iron chelators. Curr. Med. Chem. 2003,10, 1077-1084.
28. d'Hardemare Adu, M.; Alnaga, N.; Serratrice, G.; Pierre, J. L. Oxinobactin, a siderophore analogue to enterobactin involving 8hydroxyquinoline subunits: synthesis and iron binding ability. Bioorg. Med. Chem. Lett. 2008, 18, 6476-6478.
29. ten Hoeve, W.; Wynberg, H. The design of resolving agents. Chiral cyclic phosphoric acids. J. Org. Chem. 1985, 50, 4508-5414.
30. Park, J. H.; Choi, J. K.; Lee, E.; Lee, J. K.; Rhim, H.; Seo, S. H.; Kim, Y.; Doddareddy, M. R.; Pae, A. N.; Kang, J.; Roh, E. J. Lead discovery and optimization of T-type calcium channel blockers. Bioorg. Med. Chem. 2007, 15, 1409-11149
31. Briehl, H.; Lukosch, A.; Wentrup, C. Reactive nitrogenous molecules from Meldrum's acid derivatives, pyrrole-2,3-diones, and isoxazolones. J. Org. Chem. 1984, 49, 2772-2779.
32. Madrid, P. B.; Sherrill, J.; Liou, A. P.; Weisman, J. L.; Derisi, J. L.; Guy, R. K. Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities. Bioorg. Med. Chem. Lett. 2005, 15, 1015-1018.
33. 6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: potent in vivo activity in Parkinson's disease animal models. J. Med. Chem. 2009,DOI: 10.1021/jm901184n.
34. Stookey, L. Ferrozine. A new spectrophotometric reagent for iron. Anal. Chem. 1970, 42, 779-781.
35. Carter, P. Spectrophotometric determination of serum iron at the submicrogram level with a new reagent (ferrozine). Anal. Biochem. 1971, 40, 450-458.
36. Farkas, E.; Enyedy, E. A.; Zekany, L.; Deak, G. Interaction between iron(II) and hydroxamic acids: oxidation of iron(II) to iron(III) by desferrioxamine B under anaerobic conditions. J. Inorg. Biochem. 2001, 83, 107-114.
37. Halliwell, B.; Gutteridge, J. M.; Aruoma, O. I. The deoxyribose method: a simple "test-tube" assay for determination of rate constants for reactions of hydroxyl radicals. Anal. Biochem. 1987, 165, 215-219.
38. Carlsson, A.; Lindqvist, M.; Magnusson, T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 1957, 180, 1200.
39. Ungerstedt, U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 1968, 5, 107-110.
40. ten Hoeve, W.; Wynberg, H. The design of resolving agents. Chiral cyclic phosphoric acids. J. Org. Chem. 2002, 50, 4508-4514.
41. Millan, M. J.; Di Cara, B.; Hill, M.; Jackson, M.; Joyce, J. N.; Brotchie, J.; McGuire, S.; Crossman, A.; Smith, L.; Jenner, P.; Gobert, A.; Peglion, J. L.; Broceo, M. S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: II. Actions in rodent, primate, and cellular models of antiparkinsonian activity in comparison to ropinirole. J. Pharmacol. Exp. Ther. 2004, 309, 921-935.
42. McCall, R. B.; Lookingland, K. J.; Bedard, P. J.; Huff, R. M. Sumanirole, a highly dopamine D2-selective receptor agonist: in vitro and in vivo pharmacological characterization and efficacy in animal models of Parkinson's disease. J. Pharmacol. Exp. Ther. 2005, 314, 1248-1256.