The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside
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2012
Authors
Ignjatović, ĐurđicaMilutinovic, Danijela Vojnovic
Nikolić-Kokić, Aleksandra
Slavic, Marija
Andrić, Deana
Tomic, Mirko
Kostić-Rajačić, Slađana
Article (Published version)
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A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, where...as these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity. (C) 2012 Elsevier B.V. All rights reserved.
Keywords:
Arylpiperazines / Dopamine agonist / Neuroprotection / Parkinson's disease / Oxidative stressSource:
European Journal of Pharmacology, 2012, 683, 1-3, 93-100Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Biological effects, nutritional intake and status of folate and polysaturate fatty acid (PUFA): improvement of nutrition in Serbia (RS-41030)
- Structure-activity relationship of newly synthesized biological active compound (RS-172032)
DOI: 10.1016/j.ejphar.2012.03.011
ISSN: 0014-2999
PubMed: 22449382
WoS: 000303436200012
Scopus: 2-s2.0-84860456786
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Ignjatović, Đurđica AU - Milutinovic, Danijela Vojnovic AU - Nikolić-Kokić, Aleksandra AU - Slavic, Marija AU - Andrić, Deana AU - Tomic, Mirko AU - Kostić-Rajačić, Slađana PY - 2012 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1289 AB - A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity. (C) 2012 Elsevier B.V. All rights reserved. PB - Elsevier Science Bv, Amsterdam T2 - European Journal of Pharmacology T1 - The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside VL - 683 IS - 1-3 SP - 93 EP - 100 DO - 10.1016/j.ejphar.2012.03.011 ER -
@article{ author = "Ignjatović, Đurđica and Milutinovic, Danijela Vojnovic and Nikolić-Kokić, Aleksandra and Slavic, Marija and Andrić, Deana and Tomic, Mirko and Kostić-Rajačić, Slađana", year = "2012", abstract = "A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity. (C) 2012 Elsevier B.V. All rights reserved.", publisher = "Elsevier Science Bv, Amsterdam", journal = "European Journal of Pharmacology", title = "The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside", volume = "683", number = "1-3", pages = "93-100", doi = "10.1016/j.ejphar.2012.03.011" }
Ignjatović, Đ., Milutinovic, D. V., Nikolić-Kokić, A., Slavic, M., Andrić, D., Tomic, M.,& Kostić-Rajačić, S.. (2012). The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside. in European Journal of Pharmacology Elsevier Science Bv, Amsterdam., 683(1-3), 93-100. https://doi.org/10.1016/j.ejphar.2012.03.011
Ignjatović Đ, Milutinovic DV, Nikolić-Kokić A, Slavic M, Andrić D, Tomic M, Kostić-Rajačić S. The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside. in European Journal of Pharmacology. 2012;683(1-3):93-100. doi:10.1016/j.ejphar.2012.03.011 .
Ignjatović, Đurđica, Milutinovic, Danijela Vojnovic, Nikolić-Kokić, Aleksandra, Slavic, Marija, Andrić, Deana, Tomic, Mirko, Kostić-Rajačić, Slađana, "The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside" in European Journal of Pharmacology, 683, no. 1-3 (2012):93-100, https://doi.org/10.1016/j.ejphar.2012.03.011 . .