TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Sladjana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6446
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  - Elsevier
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
SP  - 117649
DO  - 10.1016/j.bmc.2024.117649
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Sladjana 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 = "Elsevier",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
pages = "117649",
doi = "10.1016/j.bmc.2024.117649"
}

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
Elsevier., 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, Sladjana 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  - Pergal, Marija V.
AU  - Brkljačić, Jelena
AU  - Tovilović-Kovačević, Gordana
AU  - Špírková, Milena
AU  - Kodranov, Igor D.
AU  - Manojlović, Dragan D.
AU  - Ostojić, Sanja B.
AU  - Knežević, Nikola Ž.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4293
AB  - Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly(dimethylsiloxane)-based macrodiol (PDMS), 4,4′-methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl)propyl methylphosphonate (FOMSN) and 2-[methoxy(polyethyleneoxy)6−9propyl]trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.
T2  - Progress in Organic Coatings
T1  - Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites
VL  - 151
SP  - 106049
DO  - 10.1016/j.porgcoat.2020.106049
ER  - 

@article{
author = "Pergal, Marija V. and Brkljačić, Jelena and Tovilović-Kovačević, Gordana and Špírková, Milena and Kodranov, Igor D. and Manojlović, Dragan D. and Ostojić, Sanja B. and Knežević, Nikola Ž.",
year = "2021",
abstract = "Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly(dimethylsiloxane)-based macrodiol (PDMS), 4,4′-methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl)propyl methylphosphonate (FOMSN) and 2-[methoxy(polyethyleneoxy)6−9propyl]trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.",
journal = "Progress in Organic Coatings",
title = "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites",
volume = "151",
pages = "106049",
doi = "10.1016/j.porgcoat.2020.106049"
}

Pergal, M. V., Brkljačić, J., Tovilović-Kovačević, G., Špírková, M., Kodranov, I. D., Manojlović, D. D., Ostojić, S. B.,& Knežević, N. Ž.. (2021). Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings, 151, 106049.
https://doi.org/10.1016/j.porgcoat.2020.106049

Pergal MV, Brkljačić J, Tovilović-Kovačević G, Špírková M, Kodranov ID, Manojlović DD, Ostojić SB, Knežević NŽ. Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings. 2021;151:106049.
doi:10.1016/j.porgcoat.2020.106049 .

Pergal, Marija V., Brkljačić, Jelena, Tovilović-Kovačević, Gordana, Špírková, Milena, Kodranov, Igor D., Manojlović, Dragan D., Ostojić, Sanja B., Knežević, Nikola Ž., "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites" in Progress in Organic Coatings, 151 (2021):106049,
https://doi.org/10.1016/j.porgcoat.2020.106049 . .

TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zagović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera S.
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5467
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.
PB  - Elsevier
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zagović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera S. and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zagović, N., Mirčić, A., Marković, Z., Todorović Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O. S., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine
Elsevier., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zagović N, Mirčić A, Marković Z, Todorović Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković OS, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zagović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera S., Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .