TY  - JOUR
AU  - Popović, Marjan
AU  - Stanojević, Željka
AU  - Tosic, Jelena
AU  - Isaković, Aleksandra
AU  - Paunović, Verica
AU  - Petricevic, Sasa
AU  - Martinović, Tamara
AU  - Ciric, Darko
AU  - Kravić-Stevović, Tamara
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
AU  - Shakib, Kaveh
AU  - Bumbasirevic, Vladimir
AU  - Trajković, Vladimir
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1812
AB  - Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.
PB  - Wiley, Hoboken
T2  - Journal of Neurochemistry
T1  - Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
VL  - 135
IS  - 1
SP  - 125
EP  - 138
DO  - 10.1111/jnc.13198
ER  - 

@article{
author = "Popović, Marjan and Stanojević, Željka and Tosic, Jelena and Isaković, Aleksandra and Paunović, Verica and Petricevic, Sasa and Martinović, Tamara and Ciric, Darko and Kravić-Stevović, Tamara and Šoškić, Vukić and Kostić Rajačić, Slađana and Shakib, Kaveh and Bumbasirevic, Vladimir and Trajković, Vladimir",
year = "2015",
abstract = "Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.",
publisher = "Wiley, Hoboken",
journal = "Journal of Neurochemistry",
title = "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats",
volume = "135",
number = "1",
pages = "125-138",
doi = "10.1111/jnc.13198"
}

Popović, M., Stanojević, Ž., Tosic, J., Isaković, A., Paunović, V., Petricevic, S., Martinović, T., Ciric, D., Kravić-Stevović, T., Šoškić, V., Kostić Rajačić, S., Shakib, K., Bumbasirevic, V.,& Trajković, V.. (2015). Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry
Wiley, Hoboken., 135(1), 125-138.
https://doi.org/10.1111/jnc.13198

Popović M, Stanojević Ž, Tosic J, Isaković A, Paunović V, Petricevic S, Martinović T, Ciric D, Kravić-Stevović T, Šoškić V, Kostić Rajačić S, Shakib K, Bumbasirevic V, Trajković V. Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry. 2015;135(1):125-138.
doi:10.1111/jnc.13198 .

Popović, Marjan, Stanojević, Željka, Tosic, Jelena, Isaković, Aleksandra, Paunović, Verica, Petricevic, Sasa, Martinović, Tamara, Ciric, Darko, Kravić-Stevović, Tamara, Šoškić, Vukić, Kostić Rajačić, Slađana, Shakib, Kaveh, Bumbasirevic, Vladimir, Trajković, Vladimir, "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats" in Journal of Neurochemistry, 135, no. 1 (2015):125-138,
https://doi.org/10.1111/jnc.13198 . .

TY  - JOUR
AU  - Senćanski, Milan
AU  - Šukalović, Vladimir
AU  - Shakib, Kaveh
AU  - Šoškić, Vukić
AU  - Došen-Mićović, Ljiljana
AU  - Kostić Rajačić, Slađana
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1504
AB  - In this paper, we report the molecular modeling of the 5HT(2A) receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT(2A) receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor-ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT(2A) receptor model, we identified key receptor-ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.
PB  - Wiley-Blackwell, Hoboken
T2  - Chemical Biology & Drug Design
T1  - Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions
VL  - 83
IS  - 4
SP  - 462
EP  - 471
DO  - 10.1111/cbdd.12261
ER  - 

@article{
author = "Senćanski, Milan and Šukalović, Vladimir and Shakib, Kaveh and Šoškić, Vukić and Došen-Mićović, Ljiljana and Kostić Rajačić, Slađana",
year = "2014",
abstract = "In this paper, we report the molecular modeling of the 5HT(2A) receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT(2A) receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor-ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT(2A) receptor model, we identified key receptor-ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Chemical Biology & Drug Design",
title = "Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions",
volume = "83",
number = "4",
pages = "462-471",
doi = "10.1111/cbdd.12261"
}

Senćanski, M., Šukalović, V., Shakib, K., Šoškić, V., Došen-Mićović, L.,& Kostić Rajačić, S.. (2014). Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions. in Chemical Biology & Drug Design
Wiley-Blackwell, Hoboken., 83(4), 462-471.
https://doi.org/10.1111/cbdd.12261

Senćanski M, Šukalović V, Shakib K, Šoškić V, Došen-Mićović L, Kostić Rajačić S. Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions. in Chemical Biology & Drug Design. 2014;83(4):462-471.
doi:10.1111/cbdd.12261 .

Senćanski, Milan, Šukalović, Vladimir, Shakib, Kaveh, Šoškić, Vukić, Došen-Mićović, Ljiljana, Kostić Rajačić, Slađana, "Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions" in Chemical Biology & Drug Design, 83, no. 4 (2014):462-471,
https://doi.org/10.1111/cbdd.12261 . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Ignjatović, Đurđica S.
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Shakib, Kaveh
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/974
AB  - It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors
VL  - 22
IS  - 12
SP  - 3967
EP  - 3972
DO  - 10.1016/j.bmcl.2012.04.098
ER  - 

@article{
author = "Šukalović, Vladimir and Ignjatović, Đurđica S. and Tovilović, Gordana and Andrić, Deana and Shakib, Kaveh and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2012",
abstract = "It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors",
volume = "22",
number = "12",
pages = "3967-3972",
doi = "10.1016/j.bmcl.2012.04.098"
}

Šukalović, V., Ignjatović, Đ. S., Tovilović, G., Andrić, D., Shakib, K., Kostić Rajačić, S.,& Šoškić, V.. (2012). Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters
Oxford : Pergamon-Elsevier Science Ltd., 22(12), 3967-3972.
https://doi.org/10.1016/j.bmcl.2012.04.098

Šukalović V, Ignjatović ĐS, Tovilović G, Andrić D, Shakib K, Kostić Rajačić S, Šoškić V. Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters. 2012;22(12):3967-3972.
doi:10.1016/j.bmcl.2012.04.098 .

Šukalović, Vladimir, Ignjatović, Đurđica S., Tovilović, Gordana, Andrić, Deana, Shakib, Kaveh, Kostić Rajačić, Slađana, Šoškić, Vukić, "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors" in Bioorganic and Medicinal Chemistry Letters, 22, no. 12 (2012):3967-3972,
https://doi.org/10.1016/j.bmcl.2012.04.098 . .