A Novel Iron(II) Preferring Dopamine Agonist Chelator as Potential Symptomatic and Neuroprotective Therapeutic Agent for Parkinson's Disease

ACS Chemical Neuroscience

Volumn 8, Issue 4, 2017, Pages 723-730

  Das, Banibrata ^a   Kandegedara, Ashoka ^a   Xu, Liping ^a   Antonio, Tamara ^b   Stemmler, Timothy ^a   Reith, Maarten E A ^b   Dutta, Aloke K ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY   (United States)

Author keywords

D2 D3 agonist; iron chelation; multifunctional drug; neuroprotection; Parkinson's disease

Indexed keywords

ANTIPARKINSON AGENT; D 607; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE RECEPTOR STIMULATING AGENT; FERROUS ION; IRON CHELATING AGENT; NEUROPROTECTIVE AGENT; PRAMIPEXOLE; RESERPINE; UNCLASSIFIED DRUG; 2,2' BIPYRIDINE; D-607 COMPOUND; PIPERAZINE DERIVATIVE;

AKINESIA; ALKYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING SITE; BLOOD BRAIN BARRIER; COMPLEX FORMATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG RECEPTOR BINDING; EMBRYO; FENTON REACTION; HUMAN; HUMAN CELL; IN VIVO STUDY; INTRINSIC ACTIVITY; IRON CHELATION; LIPID PEROXIDATION; LOCOMOTION; NERVE CELL NECROSIS; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PC12 CELL LINE; PRIORITY JOURNAL; RAT; STILLE REACTION; STOICHIOMETRY; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; DISEASE MODEL; DRUG EFFECTS; MOUSE; NERVE CELL; SYNTHESIS;

2,2'-DIPYRIDYL; ANIMALS; ANTIPARKINSON AGENTS; DISEASE MODELS, ANIMAL; DOPAMINE AGONISTS; IRON CHELATING AGENTS; MICE; NEURONS; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; PC12 CELLS; PIPERAZINES; RATS;

EID: 85018474200     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.6b00356     Document Type: Article

References (52)

1. Gelb, D. J., Oliver, E., and Gilman, S. (1999) Diagnostic criteria for Parkinson disease Arch. Neurol. 56, 33-39 10.1001/archneur.56.1.33
2. Schapira, A. H. and Olanow, C. W. (2004) Neuroprotection in Parkinson disease: mysteries, myths, and misconceptions JAMA 291, 358-364 10.1001/jama.291.3.358
3. Olanow, C. W., Stern, M. B., and Sethi, K. (2009) The scientific and clinical basis for the treatment of Parkinson disease Neurology 72, S1-136 10.1212/WNL.0b013e3181a1d44c
4. Dunnett, S. B. and Bjorklund, A. (1999) Prospects for new restorative and neuroprotective treatments in Parkinson's disease Nature 399, A32-39 10.1038/399a032
5. Dawson, T. M. and Dawson, V. L. (2003) Molecular pathways of neurodegeneration in Parkinson's disease Science 302, 819-822 10.1126/science.1087753
6. Gerlach, M., Double, K. L., Youdim, M. B., and Riederer, P. (2006) Potential sources of increased iron in the substantia nigra of parkinsonian patients J. Neural Transm. Suppl. 70, 133-142 10.1007/978-3-211-45295-0-21
7. Oakley, A. E., Collingwood, J. F., Dobson, J., Love, G., Perrott, H. R., Edwardson, J. A., Elstner, M., and Morris, C. M. (2007) Individual dopaminergic neurons show raised iron levels in Parkinson disease Neurology 68, 1820-1825 10.1212/01.wnl.0000262033.01945.9a
8. Belaidi, A. A. and Bush, A. I. (2016) Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics J. Neurochem. 139, 179-197 10.1111/jnc.13425
9. Gorell, J. M., Ordidge, R. J., Brown, G. G., Deniau, J. C., Buderer, N. M., and Helpern, J. A. (1995) Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease Neurology 45, 1138-1143 10.1212/WNL.45.6.1138
10. Berg, D. (2009) Transcranial ultrasound as a risk marker for Parkinson's disease Mov. Disord. 24, S677-683 10.1002/mds.22540
11. Zecca, L., Youdim, M. B., Riederer, P., Connor, J. R., and Crichton, R. R. (2004) Iron, brain ageing and neurodegenerative disorders Nat. Rev. Neurosci. 5, 863-873 10.1038/nrn1537
12. Ostrerova-Golts, N., Petrucelli, L., Hardy, J., Lee, J. M., Farer, M., and Wolozin, B. (2000) The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity J. Neurosci. 20, 6048-6054
13. Bharathi, Indi, S. S., and Rao, K. S. (2007) Copper- and iron-induced differential fibril formation in alpha-synuclein: TEM study Neurosci. Lett. 424, 78-82 10.1016/j.neulet.2007.06.052
14. Li, X., Jankovic, J., and Le, W. (2011) Iron chelation and neuroprotection in neurodegenerative diseases J. Neural Transm. 118, 473-477 10.1007/s00702-010-0518-0
15. Schapira, A., Bate, G., and Kirkpatrick, P. (2005) Rasagiline Nat. Rev. Drug Discovery 4, 625-626 10.1038/nrd1803
16. Marsden, C. D. and Parkes, J. D. (1976) ″On-off″ effects in patients with Parkinson's disease on chronic levodopa therapy Lancet 307, 292-296 10.1016/S0140-6736(76)91416-1
17. Stocchi, F. and Olanow, C. W. (2003) Neuroprotection in Parkinson's disease: clinical trials Ann. Neurol. 53, S87-97 discussion S97-89. 10.1002/ana.10488
18. Mandel, S., Grunblatt, E., Riederer, P., Gerlach, M., Levites, Y., and Youdim, M. B. (2003) Neuroprotective strategies in Parkinson's disease: an update on progress CNS Drugs 17, 729-762 10.2165/00023210-200317100-00004
19. Youdim, M. B. (2013) Multi target neuroprotective and neurorestorative anti-Parkinson and anti-Alzheimer drugs ladostigil and m30 derived from rasagiline Exp. Neurobiol. 22, 1-10 10.5607/en.2013.22.1.1
20. Youdim, M. B. and Oh, Y. J. (2013) Promise of neurorestoration and mitochondrial biogenesis in Parkinson's disease with multi target drugs: an alternative to stem cell therapy Exp. Neurobiol. 22, 167-172 10.5607/en.2013.22.3.167
21. Biswas, S., Hazeldine, S., Ghosh, B., Parrington, I., Kuzhikandathil, E., Reith, M. E., and Dutta, A. K. (2008) 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. 51, 3005-3019 10.1021/jm701524h
22. Ghosh, B., Antonio, T., Reith, M. E., and Dutta, A. K. (2010) Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl) (propyl)amino)ethyl)piperaz in-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 J. Med. Chem. 53, 2114-2125 10.1021/jm901618d
23. Gogoi, S., Antonio, T., Rajagopalan, S., Reith, M., Andersen, J., and Dutta, A. K. (2011) Dopamine D(2)/D(3) agonists with potent iron chelation, antioxidant and neuroprotective properties: potential implication in symptomatic and neuroprotective treatment of Parkinson's disease ChemMedChem 6, 991-995 10.1002/cmdc.201100140
24. Modi, G., Voshavar, C., Gogoi, S., Shah, M., Antonio, T., Reith, M. E., and Dutta, A. K. (2014) Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: modulator of toxicity of alpha-synuclein aggregates ACS Chem. Neurosci. 5, 700-717 10.1021/cn500084x
25. Santra, S., Xu, L., Shah, M., Johnson, M., and Dutta, A. (2013) D-512 and D-440 as novel multifunctional dopamine agonists: characterization of neuroprotection properties and evaluation of in vivo efficacy in a Parkinson's disease animal model ACS Chem. Neurosci. 4, 1382-1392 10.1021/cn400106n
26. Das, B., Vedachalam, S., Luo, D., Antonio, T., Reith, M. E., and Dutta, A. K. (2015) Development of a highly potent D2/D3 agonist and a partial agonist from structure-activity relationship study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydroben zo[d]thiazole-2,6-diamine analogues: implication in the treatment of Parkinson's disease J. Med. Chem. 58, 9179-9195 10.1021/acs.jmedchem.5b01031
27. Devos, D., Moreau, C., Devedjian, J. C., Kluza, J., Petrault, M., Laloux, C., Jonneaux, A., Ryckewaert, G., Garcon, G., Rouaix, N., Duhamel, A., Jissendi, P., Dujardin, K., Auger, F., Ravasi, L., Hopes, L., Grolez, G., Firdaus, W., Sablonniere, B., Strubi-Vuillaume, I., Zahr, N., Destee, A., Corvol, J. C., Poltl, D., Leist, M., Rose, C., Defebvre, L., Marchetti, P., Cabantchik, Z. I., and Bordet, R. (2014) Targeting chelatable iron as a therapeutic modality in Parkinson's disease Antioxid. Redox Signaling 21, 195-210 10.1089/ars.2013.5593
28. Grolez, G., Moreau, C., Sablonniere, B., Garcon, G., Devedjian, J. C., Meguig, S., Gele, P., Delmaire, C., Bordet, R., Defebvre, L., Cabantchik, I. Z., and Devos, D. (2015) Ceruloplasmin activity and iron chelation treatment of patients with Parkinson's disease BMC Neurol. 15, 74-79 10.1186/s12883-015-0331-3
29. Kaur, D., Yantiri, F., Rajagopalan, S., Kumar, J., Mo, J. Q., Boonplueang, R., Viswanath, V., Jacobs, R., Yang, L., Beal, M. F., DiMonte, D., Volitaskis, I., Ellerby, L., Cherny, R. A., Bush, A. I., and Andersen, J. K. (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease Neuron 37, 899-909 10.1016/S0896-6273(03)00126-0
30. Finkelstein, D. I., Hare, D. J., Billings, J. L., Sedjahtera, A., Nurjono, M., Arthofer, E., George, S., Culvenor, J. G., Bush, A. I., and Adlard, P. A. (2016) Clioquinol improves cognitive, motor function, and microanatomy of the alpha-synuclein hA53T transgenic mice ACS Chem. Neurosci. 7, 119-129 10.1021/acschemneuro.5b00253
31. Dutta, A. K., Venkataraman, S. K., Fei, X. S., Kolhatkar, R., Zhang, S., and Reith, M. E. (2004) Synthesis and biological characterization of novel hybrid 7-[[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino]-5,6,7,8-tetrahydro-naphthale n-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors Bioorg. Med. Chem. 12, 4361-4373 10.1016/j.bmc.2004.06.019
32. Romeo, A. M., Christen, L., Niles, E. G., and Kosman, D. J. (2001) Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: ribonucleotide reductase maturation as a probe of intracellular iron pools J. Biol. Chem. 276, 24301-24308 10.1074/jbc.M010806200
33. Baxendale, J. H. and George, P. (1950) Equilibria in solutions of ferrous ions and αα′-dipyridyl Trans. Faraday Soc. 46, 55-63 10.1039/TF9504600055
34. Breuer, W., Epsztejn, S., and Cabantchik, Z. I. (1995) Iron acquired from transferrin by K562 cells is delivered into a cytoplasmic pool of chelatable iron(II) J. Biol. Chem. 270, 24209-24215 10.1074/jbc.270.41.24209
35. Cabantchik, Z. I., Glickstein, H., Milgram, P., and Breuer, W. (1996) A fluorescence assay for assessing chelation of intracellular iron in a membrane model system and in mammalian cells Anal. Biochem. 233, 221-227 10.1006/abio.1996.0032
36. Weinreb, O., Mandel, S., Youdim, M. B., and Amit, T. (2013) Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators Free Radical Biol. Med. 62, 52-64 10.1016/j.freeradbiomed.2013.01.017
37. Rouault, T. A. and Cooperman, S. (2006) Brain iron metabolism Semin. Pediatr. Neurol. 13, 142-148 10.1016/j.spen.2006.08.002
38. Pefkianakis, E. K., Tzanetos, N. P., and Kallitsis, J. K. (2008) Synthesis and characterization of a novel vinyl-2,2-bipyridine monomer and its homopolymeric/copolymeric metal complexes Chem. Mater. 20, 6254-6262 10.1021/cm800911y
39. Schneider, C. S. and Mierau, J. (1987) Dopamine autoreceptor agonists: resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine J. Med. Chem. 30, 494-498 10.1021/jm00386a009
40. Biswas, S., Zhang, S., Fernandez, F., Ghosh, B., Zhen, J., Kuzhikandathil, E., Reith, M. E., and Dutta, A. K. (2008) Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-o l analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action J. Med. Chem. 51, 101-117 10.1021/jm070860r
41. Ghosh, B., Antonio, T., Gopishetty, B., Reith, M., and Dutta, A. (2010) Further delineation of hydrophobic binding sites in dopamine D(2)/D(3) receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthale n-2-ol Bioorg. Med. Chem. 18, 5661-5674 10.1016/j.bmc.2010.06.025
42. Kuzmic, P. (1996) Program DYNAFIT for the analysis of enzyme kinetic data: application to HIV proteinase Anal. Biochem. 237, 260-273 10.1006/abio.1996.0238
43. Jonas, S. K. and Riley, P. A. (1991) The effect of ligands on the uptake of iron by cells in culture Cell Biochem. Funct. 9, 245-253 10.1002/cbf.290090406
44. Oubidar, M., Boquillon, M., Marie, C., Bouvier, C., Beley, A., and Bralet, J. (1996) Effect of intracellular iron loading on lipid peroxidation of brain slices Free Radical Biol. Med. 21, 763-769 10.1016/0891-5849(96)00173-6
45. Arai, H., Kogure, K., Sugioka, K., and Nakano, M. (1987) Importance of two iron-reducing systems in lipid peroxidation of rat brain: implications for oxygen toxicity in the central nervous system Biochem. Int. 14, 741-749
46. Demougeot, C., Marie, C., and Beley, A. (2000) Importance of iron location in iron-induced hydroxyl radical production by brain slices Life Sci. 67, 399-410 10.1016/S0024-3205(00)00638-X
47. Methy, D., Bertrand, N., Prigent-Tessier, A., Stanimirovic, D., Beley, A., and Marie, C. (2004) Differential MnSOD and HO-1 expression in cerebral endothelial cells in response to sublethal oxidative stress Brain Res. 1003, 151-158 10.1016/j.brainres.2003.12.031
48. Carlsson, A., Lindqvist, M., and Magnusson, T. (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists Nature 180, 1200 10.1038/1801200a0
49. Gossel, M., Schmidt, W. J., Loscher, W., Zajaczkowski, W., and Danysz, W. (1995) Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats J. Neural Transm.: Parkinson's Dis. Dementia Sect. 10, 27-39 10.1007/BF02256627
50. McCall, R. B., Lookingland, K. J., Bedard, P. J., and Huff, R. M. (2005) 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. 314, 1248-1256 10.1124/jpet.105.084202
51. Ferger, B., Buck, K., Shimasaki, M., Koros, E., Voehringer, P., and Buerger, E. (2010) Continuous dopaminergic stimulation by pramipexole is effective to treat early morning akinesia in animal models of Parkinson's disease: A pharmacokinetic-pharmacodynamic study using in vivo microdialysis in rats Synapse 64, 533-541 10.1002/syn.20759
52. Singh, N., Haldar, S., Tripathi, A. K., Horback, K., Wong, J., Sharma, D., Beserra, A., Suda, S., Anbalagan, C., Dev, S., Mukhopadhyay, C. K., and Singh, A. (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities Antioxid. Redox Signaling 20, 1324-1363 10.1089/ars.2012.4931