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  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Ignjatović, Đurđica
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2255
AB  - The dopaminergic receptor system has been the focus for the development
   of new pharmacotherapeutic agents targeting a number of central nervous
   system related disorders, such as drug addiction, schizophrenia,
   depression, and Parkinson's disease, to name just a few. To date, the
   crystal structure for the human D2 receptor is not known, despite its
   vital function and importance as a therapeutic target. Herein, a recent
   advancement in the determination of key receptor ligand interactions for
   the available arylpiperazine-like ligands, using a D2 receptor model
   based on the crystal structure of the D3 receptor is presented. To
   determine key interactions responsible for high dopaminergic activity,
   computer-docking analysis was used together with experimental data. A
   total of 4 dopaminergic ligands showing moderate to high affinity were
   tested and the obtained results rationalized using ligand structures
   docked into the proposed D2 receptor model.
T2  - Journal of the Serbian Chemical Society
T1  - Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides
IS  - 12
VL  - 79
DO  - 10.2298/JSC140423070S
SP  - 1461
EP  - 1467
ER  - 

@article{
author = "Šukalović, Vladimir and Šoškić, Vukić and Ignjatović, Đurđica and Andrić, Deana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2014",
abstract = "The dopaminergic receptor system has been the focus for the development
   of new pharmacotherapeutic agents targeting a number of central nervous
   system related disorders, such as drug addiction, schizophrenia,
   depression, and Parkinson's disease, to name just a few. To date, the
   crystal structure for the human D2 receptor is not known, despite its
   vital function and importance as a therapeutic target. Herein, a recent
   advancement in the determination of key receptor ligand interactions for
   the available arylpiperazine-like ligands, using a D2 receptor model
   based on the crystal structure of the D3 receptor is presented. To
   determine key interactions responsible for high dopaminergic activity,
   computer-docking analysis was used together with experimental data. A
   total of 4 dopaminergic ligands showing moderate to high affinity were
   tested and the obtained results rationalized using ligand structures
   docked into the proposed D2 receptor model.",
journal = "Journal of the Serbian Chemical Society",
title = "Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides",
number = "12",
volume = "79",
doi = "10.2298/JSC140423070S",
pages = "1461-1467"
}

Šukalović, V., Šoškić, V., Ignjatović, Đ., Andrić, D., Penjišević, J.,& Kostić-Rajačić, S.. (2014). Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides. in Journal of the Serbian Chemical Society, 79(12), 1461-1467.
https://doi.org/10.2298/JSC140423070S

Šukalović V, Šoškić V, Ignjatović Đ, Andrić D, Penjišević J, Kostić-Rajačić S. Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides. in Journal of the Serbian Chemical Society. 2014;79(12):1461-1467.
doi:10.2298/JSC140423070S .

Šukalović, Vladimir, Šoškić, Vukić, Ignjatović, Đurđica, Andrić, Deana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides" in Journal of the Serbian Chemical Society, 79, no. 12 (2014):1461-1467,
https://doi.org/10.2298/JSC140423070S . .