TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Šoškić, Vukić
AU  - Schrattenholz, Andre
AU  - Kostić-Rajačić, Slađana
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Arsikin, Katarina
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6343
AB  - We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SHSY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3b gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERK and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-OHDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.
PB  - Elsevier Ltd.
T2  - Neuropharmacology
T1  - Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death
VL  - 72
DO  - 10.1016/j.neuropharm.2013.04.037
SP  - 224
EP  - 235
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Šoškić, Vukić and Schrattenholz, Andre and Kostić-Rajačić, Slađana and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Arsikin, Katarina and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2013",
abstract = "We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SHSY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3b gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERK and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-OHDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.",
publisher = "Elsevier Ltd.",
journal = "Neuropharmacology",
title = "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death",
volume = "72",
doi = "10.1016/j.neuropharm.2013.04.037",
pages = "224-235"
}

Tovilović-Kovačević, G., Zogović, N., Šoškić, V., Schrattenholz, A., Kostić-Rajačić, S., Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Arsikin, K., Harhaji-Trajković, L.,& Trajković, V.. (2013). Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology
Elsevier Ltd.., 72, 224-235.
https://doi.org/10.1016/j.neuropharm.2013.04.037

Tovilović-Kovačević G, Zogović N, Šoškić V, Schrattenholz A, Kostić-Rajačić S, Misirkić Marjanović M, Janjetović K, Vučićević L, Arsikin K, Harhaji-Trajković L, Trajković V. Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology. 2013;72:224-235.
doi:10.1016/j.neuropharm.2013.04.037 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Šoškić, Vukić, Schrattenholz, Andre, Kostić-Rajačić, Slađana, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Arsikin, Katarina, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death" in Neuropharmacology, 72 (2013):224-235,
https://doi.org/10.1016/j.neuropharm.2013.04.037 . .

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Kostić-Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6367
AB  - The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D₁/D₂ receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.
PB  - John Wiley and Sons
T2  - ChemMedChem
T1  - Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis
IS  - 3
VL  - 7
DO  - 10.1002/cmdc.201100537
SP  - 495
EP  - 508
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Harhaji-Trajković, Ljubica and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Kostić-Rajačić, Slađana and Schrattenholz, Andre and Isaković, Aleksandra and Šoškić, Vukić and Trajković, Vladimir",
year = "2012",
abstract = "The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D₁/D₂ receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.",
publisher = "John Wiley and Sons",
journal = "ChemMedChem",
title = "Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis",
number = "3",
volume = "7",
doi = "10.1002/cmdc.201100537",
pages = "495-508"
}

Tovilović-Kovačević, G., Zogović, N., Harhaji-Trajković, L., Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Kostić-Rajačić, S., Schrattenholz, A., Isaković, A., Šoškić, V.,& Trajković, V.. (2012). Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis. in ChemMedChem
John Wiley and Sons., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537

Tovilović-Kovačević G, Zogović N, Harhaji-Trajković L, Misirkić Marjanović M, Janjetović K, Vučićević L, Kostić-Rajačić S, Schrattenholz A, Isaković A, Šoškić V, Trajković V. Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis. in ChemMedChem. 2012;7(3):495-508.
doi:10.1002/cmdc.201100537 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Harhaji-Trajković, Ljubica, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Kostić-Rajačić, Slađana, Schrattenholz, Andre, Isaković, Aleksandra, Šoškić, Vukić, Trajković, Vladimir, "Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis" in ChemMedChem, 7, no. 3 (2012):495-508,
https://doi.org/10.1002/cmdc.201100537 . .

TY  - JOUR
AU  - Andrić, Deana
AU  - Tovilović-Kovačević, Gordana
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Tomić, Mirko
AU  - Kostić-Rajačić, Slađana V.
PY  - 2007
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/554
AB  - Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. .
AB  - Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .
T2  - Journal of the Serbian Chemical Society
T1  - 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje
T1  - 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation
IS  - 8-9
VL  - 72
DO  - 10.2298/JSC0709747A
SP  - 747
EP  - 755
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_554
ER  - 

@article{
author = "Andrić, Deana and Tovilović-Kovačević, Gordana and Roglić, Goran and Šoškić, Vukić and Tomić, Mirko and Kostić-Rajačić, Slađana V.",
year = "2007, 2007",
abstract = "Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. ., Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .",
journal = "Journal of the Serbian Chemical Society",
title = "6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje, 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation",
number = "8-9",
volume = "72",
doi = "10.2298/JSC0709747A",
pages = "747-755",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_554"
}

Andrić, D., Tovilović-Kovačević, G., Roglić, G., Šoškić, V., Tomić, M.,& Kostić-Rajačić, S. V.. (2007). 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje. in Journal of the Serbian Chemical Society, 72(8-9), 747-755.
https://doi.org/10.2298/JSC0709747A
https://hdl.handle.net/21.15107/rcub_ibiss_554

Andrić D, Tovilović-Kovačević G, Roglić G, Šoškić V, Tomić M, Kostić-Rajačić SV. 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje. in Journal of the Serbian Chemical Society. 2007;72(8-9):747-755.
doi:10.2298/JSC0709747A
https://hdl.handle.net/21.15107/rcub_ibiss_554 .

Andrić, Deana, Tovilović-Kovačević, Gordana, Roglić, Goran, Šoškić, Vukić, Tomić, Mirko, Kostić-Rajačić, Slađana V., "6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje" in Journal of the Serbian Chemical Society, 72, no. 8-9 (2007):747-755,
https://doi.org/10.2298/JSC0709747A .,
https://hdl.handle.net/21.15107/rcub_ibiss_554 .

TY  - JOUR
AU  - Andrić, Deana
AU  - Tovilović-Kovačević, Gordana
AU  - Roglić, Goran
AU  - Ignjatović, Đurđica
AU  - Šoškić, Vukić
AU  - Tomić, Mirko
AU  - Kostić-Rajačić, Slađana V.
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/553
AB  - Six newly synthesized heterocyclic (2-nitrophenyl)piperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and _1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pK i values). Compound 7c, 4-bromo-6-{2-_4-(2-nitrophenyl)piperazin- 1-yl_ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations.
AB  - Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike (>1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.
PB  - Belgrade: Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina
T1  - Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives
IS  - 5
VL  - 72
DO  - 10.2298/JSC0705429A
SP  - 429
EP  - 435
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_553
ER  - 

@article{
author = "Andrić, Deana and Tovilović-Kovačević, Gordana and Roglić, Goran and Ignjatović, Đurđica and Šoškić, Vukić and Tomić, Mirko and Kostić-Rajačić, Slađana V.",
year = "2007",
abstract = "Six newly synthesized heterocyclic (2-nitrophenyl)piperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and _1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pK i values). Compound 7c, 4-bromo-6-{2-_4-(2-nitrophenyl)piperazin- 1-yl_ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations., Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike (>1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina, Synthesis and pharmacological evaluation of several N-(2-nitrophenyl) piperazine derivatives",
number = "5",
volume = "72",
doi = "10.2298/JSC0705429A",
pages = "429-435",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_553"
}

Andrić, D., Tovilović-Kovačević, G., Roglić, G., Ignjatović, Đ., Šoškić, V., Tomić, M.,& Kostić-Rajačić, S. V.. (2007). Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina. in Journal of the Serbian Chemical Society
Belgrade: Serbian Chemical Society., 72(5), 429-435.
https://doi.org/10.2298/JSC0705429A
https://hdl.handle.net/21.15107/rcub_ibiss_553

Andrić D, Tovilović-Kovačević G, Roglić G, Ignjatović Đ, Šoškić V, Tomić M, Kostić-Rajačić SV. Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina. in Journal of the Serbian Chemical Society. 2007;72(5):429-435.
doi:10.2298/JSC0705429A
https://hdl.handle.net/21.15107/rcub_ibiss_553 .

Andrić, Deana, Tovilović-Kovačević, Gordana, Roglić, Goran, Ignjatović, Đurđica, Šoškić, Vukić, Tomić, Mirko, Kostić-Rajačić, Slađana V., "Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina" in Journal of the Serbian Chemical Society, 72, no. 5 (2007):429-435,
https://doi.org/10.2298/JSC0705429A .,
https://hdl.handle.net/21.15107/rcub_ibiss_553 .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Šukalović, Vladimir B.
AU  - Tasić, Bosiljka
AU  - Kostić-Rajačić, Slađana V.
AU  - Šoškić, Vukić
PY  - 2002
PY  - 2002
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/18
AB  - In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding.
AB  - U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor.
PB  - Društvo medicinskih biohemičara Srbije i Crne Gore
T2  - Yugoslav Medical Biochemistry
T1  - Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena
T1  - Interaction of different third intracellular loop fragments of human dopamine d2l receptor with a-subunit of gi1 protein - prospective therapeutic application
IS  - 1
VL  - 21
DO  - 10.2298/JMH0201009I
SP  - 9
EP  - 14
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_18
ER  - 

@article{
author = "Ignjatović, Đurđica and Šukalović, Vladimir B. and Tasić, Bosiljka and Kostić-Rajačić, Slađana V. and Šoškić, Vukić",
year = "2002, 2002",
abstract = "In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding., U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor.",
publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore",
journal = "Yugoslav Medical Biochemistry",
title = "Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena, Interaction of different third intracellular loop fragments of human dopamine d2l receptor with a-subunit of gi1 protein - prospective therapeutic application",
number = "1",
volume = "21",
doi = "10.2298/JMH0201009I",
pages = "9-14",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_18"
}

Ignjatović, Đ., Šukalović, V. B., Tasić, B., Kostić-Rajačić, S. V.,& Šoškić, V.. (2002). Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena. in Yugoslav Medical Biochemistry
Društvo medicinskih biohemičara Srbije i Crne Gore., 21(1), 9-14.
https://doi.org/10.2298/JMH0201009I
https://hdl.handle.net/21.15107/rcub_ibiss_18

Ignjatović Đ, Šukalović VB, Tasić B, Kostić-Rajačić SV, Šoškić V. Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena. in Yugoslav Medical Biochemistry. 2002;21(1):9-14.
doi:10.2298/JMH0201009I
https://hdl.handle.net/21.15107/rcub_ibiss_18 .

Ignjatović, Đurđica, Šukalović, Vladimir B., Tasić, Bosiljka, Kostić-Rajačić, Slađana V., Šoškić, Vukić, "Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena" in Yugoslav Medical Biochemistry, 21, no. 1 (2002):9-14,
https://doi.org/10.2298/JMH0201009I .,
https://hdl.handle.net/21.15107/rcub_ibiss_18 .