TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6648
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6648
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6648"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 .,
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6629
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Amsterdam: Elsevier Ltd
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Amsterdam: Elsevier Ltd",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Amsterdam: Elsevier Ltd., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 . .

TY  - JOUR
AU  - Isaković, Aleksandra J
AU  - Janković, Teodora
AU  - Harhaji-Trajković, Ljubica
AU  - Kostić-Rajačić, Slađana V.
AU  - Nikolić, Zoran M
AU  - Vajs, Vlatka E
AU  - Trajković, Vladimir S
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1530
AB  - The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G(2)/M and G(0)/G(1) phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G(2)/M cell block and apoptotic cell death in glioma cells. (C) 2008 Elsevier Ltd. All rights reserved.
T2  - Bioorganic & Medicinal Chemistry
T1  - Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements
IS  - 10
VL  - 16
EP  - 5694
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1530
ER  - 

@article{
author = "Isaković, Aleksandra J and Janković, Teodora and Harhaji-Trajković, Ljubica and Kostić-Rajačić, Slađana V. and Nikolić, Zoran M and Vajs, Vlatka E and Trajković, Vladimir S",
year = "2008",
abstract = "The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G(2)/M and G(0)/G(1) phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G(2)/M cell block and apoptotic cell death in glioma cells. (C) 2008 Elsevier Ltd. All rights reserved.",
journal = "Bioorganic & Medicinal Chemistry",
title = "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements",
number = "10",
volume = "16",
pages = "5694",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1530"
}

Isaković, A. J., Janković, T., Harhaji-Trajković, L., Kostić-Rajačić, S. V., Nikolić, Z. M., Vajs, V. E.,& Trajković, V. S.. (2008). Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic & Medicinal Chemistry, 16(10).
https://hdl.handle.net/21.15107/rcub_ibiss_1530

Isaković AJ, Janković T, Harhaji-Trajković L, Kostić-Rajačić SV, Nikolić ZM, Vajs VE, Trajković VS. Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic & Medicinal Chemistry. 2008;16(10):null-5694.
https://hdl.handle.net/21.15107/rcub_ibiss_1530 .

Isaković, Aleksandra J, Janković, Teodora, Harhaji-Trajković, Ljubica, Kostić-Rajačić, Slađana V., Nikolić, Zoran M, Vajs, Vlatka E, Trajković, Vladimir S, "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements" in Bioorganic & Medicinal Chemistry, 16, no. 10 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1530 .

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 .