Studies of enzyme interactions with toxic and pharmacologically active molecules

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Studies of enzyme interactions with toxic and pharmacologically active molecules (en)
Истраживања интеракција ензима са токсичним и фармаколошки активним молекулима (sr)
Istraživanja interakcija enzima sa toksičnim i farmakološki aktivnim molekulima (sr_RS)
Authors

Publications

Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments

Jovanović, Maja V.; Savić, Jasmina; Kovačević, Renata; Tasić, Viša; Todorović, Žaklina; Stevanović, Svetlana; Manojlović, Dragan D.; Jovašević-Stojanović, Milena

(Elsevier, 2020)

TY  - JOUR
AU  - Jovanović, Maja V.
AU  - Savić, Jasmina
AU  - Kovačević, Renata
AU  - Tasić, Viša
AU  - Todorović, Žaklina
AU  - Stevanović, Svetlana
AU  - Manojlović, Dragan D.
AU  - Jovašević-Stojanović, Milena
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3820
AB  - Urban airborne particles contain a wide spectrum of components, known to have harmful effects on human health. This study reports a detailed investigation of fine particulate matter (PM2.5), chemical content and oxidative potential derived from two different urban environments. During summer and winter, 20-day campaigns were conducted at Belgrade city center (urban-background site – UB) and Bor (urban-industrial site – UI). Using various analytical techniques, carbonaceous compounds, water-soluble inorganic ions, major and trace elements were determined, while the oxidative potential of PM2.5 was estimated by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay (OPDCFH values). The mean PM2.5 concentrations in both urban environments were above the recommended daily value, and the dominant PM2.5 mass contributor was organic matter (29–55%). The OC/EC ratio was significantly higher at UB site during winter, which was an indication of a considerable contribution of secondary organic carbon to the overall organic carbon (OC). Water-soluble organic carbon (WSOC) was also higher at UB than at UI site, and it probably came from the same sources as OC. In general, the different partition of secondary organic aerosol (SOA) in warm and cold periods affected the number of organic components. Sulfates and nitrates were the most abundant ions at both sites and they counted approximately 40% (summer) and 50% (winter) of total ions. Further, the concentrations of the most elements, particularly some potentially carcinogenic elements such as As, Cd and Pb were significantly higher at UI, due to the emissions from the copper smelter complex in the vicinity. The mean OPDCFH values were similar during the summer at both sampling sites, whereas a statistically significant difference between sites was noticed in favor of UB environment in winter.
PB  - Elsevier
T2  - Science of the Total Environment
T1  - Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments
VL  - 708
SP  - 135209
DO  - 10.1016/j.scitotenv.2019.135209
ER  - 
@article{
author = "Jovanović, Maja V. and Savić, Jasmina and Kovačević, Renata and Tasić, Viša and Todorović, Žaklina and Stevanović, Svetlana and Manojlović, Dragan D. and Jovašević-Stojanović, Milena",
year = "2020",
abstract = "Urban airborne particles contain a wide spectrum of components, known to have harmful effects on human health. This study reports a detailed investigation of fine particulate matter (PM2.5), chemical content and oxidative potential derived from two different urban environments. During summer and winter, 20-day campaigns were conducted at Belgrade city center (urban-background site – UB) and Bor (urban-industrial site – UI). Using various analytical techniques, carbonaceous compounds, water-soluble inorganic ions, major and trace elements were determined, while the oxidative potential of PM2.5 was estimated by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay (OPDCFH values). The mean PM2.5 concentrations in both urban environments were above the recommended daily value, and the dominant PM2.5 mass contributor was organic matter (29–55%). The OC/EC ratio was significantly higher at UB site during winter, which was an indication of a considerable contribution of secondary organic carbon to the overall organic carbon (OC). Water-soluble organic carbon (WSOC) was also higher at UB than at UI site, and it probably came from the same sources as OC. In general, the different partition of secondary organic aerosol (SOA) in warm and cold periods affected the number of organic components. Sulfates and nitrates were the most abundant ions at both sites and they counted approximately 40% (summer) and 50% (winter) of total ions. Further, the concentrations of the most elements, particularly some potentially carcinogenic elements such as As, Cd and Pb were significantly higher at UI, due to the emissions from the copper smelter complex in the vicinity. The mean OPDCFH values were similar during the summer at both sampling sites, whereas a statistically significant difference between sites was noticed in favor of UB environment in winter.",
publisher = "Elsevier",
journal = "Science of the Total Environment",
title = "Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments",
volume = "708",
pages = "135209",
doi = "10.1016/j.scitotenv.2019.135209"
}
Jovanović, M. V., Savić, J., Kovačević, R., Tasić, V., Todorović, Ž., Stevanović, S., Manojlović, D. D.,& Jovašević-Stojanović, M.. (2020). Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments. in Science of the Total Environment
Elsevier., 708, 135209.
https://doi.org/10.1016/j.scitotenv.2019.135209
Jovanović MV, Savić J, Kovačević R, Tasić V, Todorović Ž, Stevanović S, Manojlović DD, Jovašević-Stojanović M. Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments. in Science of the Total Environment. 2020;708:135209.
doi:10.1016/j.scitotenv.2019.135209 .
Jovanović, Maja V., Savić, Jasmina, Kovačević, Renata, Tasić, Viša, Todorović, Žaklina, Stevanović, Svetlana, Manojlović, Dragan D., Jovašević-Stojanović, Milena, "Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments" in Science of the Total Environment, 708 (2020):135209,
https://doi.org/10.1016/j.scitotenv.2019.135209 . .
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Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

Avramović, Nataša; Mandić, Boris; Savić-Radojević, Ana; Simić, Tatjana

(2020)

TY  - JOUR
AU  - Avramović, Nataša
AU  - Mandić, Boris
AU  - Savić-Radojević, Ana
AU  - Simić, Tatjana
PY  - 2020
UR  - https://www.mdpi.com/1999-4923/12/4/298
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4021
AB  - Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review.
T2  - Pharmaceutics
T2  - Pharmaceutics
T1  - Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy
VL  - 12
IS  - 4
SP  - 298
DO  - 10.3390/pharmaceutics12040298
ER  - 
@article{
author = "Avramović, Nataša and Mandić, Boris and Savić-Radojević, Ana and Simić, Tatjana",
year = "2020",
abstract = "Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review.",
journal = "Pharmaceutics, Pharmaceutics",
title = "Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy",
volume = "12",
number = "4",
pages = "298",
doi = "10.3390/pharmaceutics12040298"
}
Avramović, N., Mandić, B., Savić-Radojević, A.,& Simić, T.. (2020). Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy. in Pharmaceutics, 12(4), 298.
https://doi.org/10.3390/pharmaceutics12040298
Avramović N, Mandić B, Savić-Radojević A, Simić T. Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy. in Pharmaceutics. 2020;12(4):298.
doi:10.3390/pharmaceutics12040298 .
Avramović, Nataša, Mandić, Boris, Savić-Radojević, Ana, Simić, Tatjana, "Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy" in Pharmaceutics, 12, no. 4 (2020):298,
https://doi.org/10.3390/pharmaceutics12040298 . .
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Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition

Đorđević, Ivana S.; Popadić, Marko; Sarvan, Mirjana; Petković-Benazzouz, Marija; Janjić, Goran V.

(Wiley, 2020)

TY  - JOUR
AU  - Đorđević, Ivana S.
AU  - Popadić, Marko
AU  - Sarvan, Mirjana
AU  - Petković-Benazzouz, Marija
AU  - Janjić, Goran V.
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3877
AB  - Statistical analysis of data from crystal structures extracted from the Cambridge Structural Database (CSD) has shown that S and Se atoms display a similar tendency towards specific types of interaction if they are part of a fragment that corresponds to the side chains of cysteine (Cys), methionine (Met) selenocysteine (Sec) and selenomethionine (Mse). The most numerous are structures with C-H..Se and C-H..S interactions (∼80%), notably less numerous are structures with Se..Se and S..S interactions (∼5%), and Se..π and S..π interactions are the least numerous. The results of quantum-chemical calculations have indicated that C-H..Se (∼-0.8 kcal mol-1) and C-H..S interactions are weaker than the most stable parallel interaction (∼-3.3 kcal mol-1) and electrostatic interactions of σ/π type (∼-2.6 kcal mol-1). Their significant presence can be explained by the abundance of CH groups compared with the numbers of Se and S atoms in the crystal structures, and also by the influence of substituents bonded to the Se or S atom that further reduce their possibilities for interacting with species from the environment. This can also offer an explanation as to why O-H..Se (∼-4.4 kcal mol-1) and N-H..Se interactions (∼-2.2 kcal mol-1) are less numerous. Docking studies revealed that S and Se rarely participate in interactions with the amino acid residues of target enzymes, mostly because those residues preferentially interact with the substituents bonded to Se and S. The differences between Se and S ligands in the number and positions of their binding sites are more pronounced if the substituents are polar and if there are more Se/S atoms in the ligand. © 2020 International Union of Crystallography.
PB  - Wiley
T2  - Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials
T1  - Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition
VL  - 76
IS  - 1
SP  - 122
EP  - 136
DO  - 10.1107/S2052520619016287
ER  - 
@article{
author = "Đorđević, Ivana S. and Popadić, Marko and Sarvan, Mirjana and Petković-Benazzouz, Marija and Janjić, Goran V.",
year = "2020",
abstract = "Statistical analysis of data from crystal structures extracted from the Cambridge Structural Database (CSD) has shown that S and Se atoms display a similar tendency towards specific types of interaction if they are part of a fragment that corresponds to the side chains of cysteine (Cys), methionine (Met) selenocysteine (Sec) and selenomethionine (Mse). The most numerous are structures with C-H..Se and C-H..S interactions (∼80%), notably less numerous are structures with Se..Se and S..S interactions (∼5%), and Se..π and S..π interactions are the least numerous. The results of quantum-chemical calculations have indicated that C-H..Se (∼-0.8 kcal mol-1) and C-H..S interactions are weaker than the most stable parallel interaction (∼-3.3 kcal mol-1) and electrostatic interactions of σ/π type (∼-2.6 kcal mol-1). Their significant presence can be explained by the abundance of CH groups compared with the numbers of Se and S atoms in the crystal structures, and also by the influence of substituents bonded to the Se or S atom that further reduce their possibilities for interacting with species from the environment. This can also offer an explanation as to why O-H..Se (∼-4.4 kcal mol-1) and N-H..Se interactions (∼-2.2 kcal mol-1) are less numerous. Docking studies revealed that S and Se rarely participate in interactions with the amino acid residues of target enzymes, mostly because those residues preferentially interact with the substituents bonded to Se and S. The differences between Se and S ligands in the number and positions of their binding sites are more pronounced if the substituents are polar and if there are more Se/S atoms in the ligand. © 2020 International Union of Crystallography.",
publisher = "Wiley",
journal = "Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials",
title = "Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition",
volume = "76",
number = "1",
pages = "122-136",
doi = "10.1107/S2052520619016287"
}
Đorđević, I. S., Popadić, M., Sarvan, M., Petković-Benazzouz, M.,& Janjić, G. V.. (2020). Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition. in Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials
Wiley., 76(1), 122-136.
https://doi.org/10.1107/S2052520619016287
Đorđević IS, Popadić M, Sarvan M, Petković-Benazzouz M, Janjić GV. Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition. in Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials. 2020;76(1):122-136.
doi:10.1107/S2052520619016287 .
Đorđević, Ivana S., Popadić, Marko, Sarvan, Mirjana, Petković-Benazzouz, Marija, Janjić, Goran V., "Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition" in Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials, 76, no. 1 (2020):122-136,
https://doi.org/10.1107/S2052520619016287 . .
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Platinum and ruthenium complexes as promising molecules in cancer therapy

Avramović, Nataša; Ignjatović, Nikola; Savić, Aleksandar

(Srpsko lekarsko društvo, 2019)

TY  - JOUR
AU  - Avramović, Nataša
AU  - Ignjatović, Nikola
AU  - Savić, Aleksandar
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3304
AB  - Cancer is one of the most common fatal diseases in humans nowadays. About 20 million new cancer cases are expected in the next two decades worldwide. The development of new chemotherapeutic agents with improved properties is presently the main challenge in the medicinal chemistry. Cisplatin was introduced to oncology in 1978 as first chemotherapeutic agent regarding its specific interaction with DNA, leading to its damage and causing the cell death. Since the first application of cisplatin in cancer therapy, there has been a growing interest in new metal-based compounds, in particular platinum and ruthenium complexes, with better anticancer activity and less side-effects compared to cisplatin. Carboplatin and oxaliplatin have shown promising action against some types of cancer, which are resistant to cisplatin. With the aim to overcome cross-resistance to these Pt(II) drugs, bioavailable platinum complexes (satraplatin and picoplatin) firstly found application as orally administered drugs, as well as some combined therapies of Pt(II) drugs (cisplatin, picoplatin) with specific resistant modulators. In recent years, novel polymer and liposomal formulations of platinum drugs (prolindac, lipoplatin, lipoxal, aroplatin) have been designed with strategy to improve drug delivery to target cancer cells and reduce toxicity. Complexes based on ruthenium have great potential to become leading candidates for the medical use in anticancer therapy. Some of these compounds have shown good anticancer activity, both in vitro and in vivo and two of them (KP1019 and NAMI-A) have passed clinical trials and given promising results.
PB  - Srpsko lekarsko društvo
T2  - Srpski Arhiv za Celokupno Lekarstvo
T1  - Platinum and ruthenium complexes as promising molecules in cancer therapy
VL  - 147
IS  - 1-2
SP  - 105
EP  - 109
DO  - 10.2298/SARH180706075A
ER  - 
@article{
author = "Avramović, Nataša and Ignjatović, Nikola and Savić, Aleksandar",
year = "2019",
abstract = "Cancer is one of the most common fatal diseases in humans nowadays. About 20 million new cancer cases are expected in the next two decades worldwide. The development of new chemotherapeutic agents with improved properties is presently the main challenge in the medicinal chemistry. Cisplatin was introduced to oncology in 1978 as first chemotherapeutic agent regarding its specific interaction with DNA, leading to its damage and causing the cell death. Since the first application of cisplatin in cancer therapy, there has been a growing interest in new metal-based compounds, in particular platinum and ruthenium complexes, with better anticancer activity and less side-effects compared to cisplatin. Carboplatin and oxaliplatin have shown promising action against some types of cancer, which are resistant to cisplatin. With the aim to overcome cross-resistance to these Pt(II) drugs, bioavailable platinum complexes (satraplatin and picoplatin) firstly found application as orally administered drugs, as well as some combined therapies of Pt(II) drugs (cisplatin, picoplatin) with specific resistant modulators. In recent years, novel polymer and liposomal formulations of platinum drugs (prolindac, lipoplatin, lipoxal, aroplatin) have been designed with strategy to improve drug delivery to target cancer cells and reduce toxicity. Complexes based on ruthenium have great potential to become leading candidates for the medical use in anticancer therapy. Some of these compounds have shown good anticancer activity, both in vitro and in vivo and two of them (KP1019 and NAMI-A) have passed clinical trials and given promising results.",
publisher = "Srpsko lekarsko društvo",
journal = "Srpski Arhiv za Celokupno Lekarstvo",
title = "Platinum and ruthenium complexes as promising molecules in cancer therapy",
volume = "147",
number = "1-2",
pages = "105-109",
doi = "10.2298/SARH180706075A"
}
Avramović, N., Ignjatović, N.,& Savić, A.. (2019). Platinum and ruthenium complexes as promising molecules in cancer therapy. in Srpski Arhiv za Celokupno Lekarstvo
Srpsko lekarsko društvo., 147(1-2), 105-109.
https://doi.org/10.2298/SARH180706075A
Avramović N, Ignjatović N, Savić A. Platinum and ruthenium complexes as promising molecules in cancer therapy. in Srpski Arhiv za Celokupno Lekarstvo. 2019;147(1-2):105-109.
doi:10.2298/SARH180706075A .
Avramović, Nataša, Ignjatović, Nikola, Savić, Aleksandar, "Platinum and ruthenium complexes as promising molecules in cancer therapy" in Srpski Arhiv za Celokupno Lekarstvo, 147, no. 1-2 (2019):105-109,
https://doi.org/10.2298/SARH180706075A . .
1
1
1

Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro

Lazovic, Sasa; Leskovac, Andreja; Petrović, Sandra; Šenerović, Lidija; Krivokapic, Nevena; Mitrovic, Tatjana; Bozovic, Nikola; Vasic, Vesna; Nikodinović-Runić, Jasmina

(Elsevier Gmbh, Urban & Fischer Verlag, Jena, 2017)

TY  - JOUR
AU  - Lazovic, Sasa
AU  - Leskovac, Andreja
AU  - Petrović, Sandra
AU  - Šenerović, Lidija
AU  - Krivokapic, Nevena
AU  - Mitrovic, Tatjana
AU  - Bozovic, Nikola
AU  - Vasic, Vesna
AU  - Nikodinović-Runić, Jasmina
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2373
AB  - It is known that some bacterial species are more resilient to different kinds of irradiation due to the naturally developed protective mechanisms and compounds such as pigments. On the other hand, reasoned tissue engineering using plasma remains a critical task and requires very precise control of plasma parameters in order to mitigate its potential detrimental effects. Here we isolated a natural protective agent, microbially produced undecylprodigiosin ((5'2)-4'-methoxy-5'-[(5-undecy1-1H-pyrrol2-yl)methylenel-1H,5'H-2,2'-bipyrrole), and investigated its effects on human blood cells independently and in combination with plasma. Two apprOaches were applied; the first, undecylprodigiosin (UP pigment) was added to the blood cultures, which then were exposed to plasma (pre-treatment); and the second- the blood cultures were exposed to plasma and then treated with pigment (post-treatment). The interactions of plasma and UP pigment with blood cells were investigated by conducting a series of biological tests providing the information regarding their genotoxicity, cytotoxicity and redox modulating activities. The exposure of cells to plasma induced oxidative stress as well as certain genotoxic and cytotoxic effects seen as elevated micronuclei incidence, decreased cell proliferation and enhanced apoptosis. In blood cultures treated with UP pigment alone, we found that both cytotoxic and protective effects could be induced depending on the concentration used. The highest UP pigment concentration increased lipid peroxidation and the incidence of micronuclei by more than 70% with maximal suppression of cell proliferation. On the contrary, we found that the lowest UP pigment concentration displayed protective effects. In combined treatments with plasma and UP pigment, we found that UP pigment could provide spatial shielding to plasma exposure. In the pre-treatment approach, the incidence of micronuclei was reduced by 35.52% compared to control while malondialdehyde level decreased by 36% indicating a significant mitigation of membrane damage induced by plasma. These results open perspectives for utilizing UP pigment for protection against overexposures in the field of plasma medicine. (C) 2016 Elsevier GmbH. All rights reserved.
PB  - Elsevier Gmbh, Urban & Fischer Verlag, Jena
T2  - Experimental and Toxicologic Pathology
T1  - Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro
VL  - 69
IS  - 1
SP  - 55
EP  - 62
DO  - 10.1016/j.etp.2016.11.003
UR  - Kon_3189
ER  - 
@article{
author = "Lazovic, Sasa and Leskovac, Andreja and Petrović, Sandra and Šenerović, Lidija and Krivokapic, Nevena and Mitrovic, Tatjana and Bozovic, Nikola and Vasic, Vesna and Nikodinović-Runić, Jasmina",
year = "2017",
abstract = "It is known that some bacterial species are more resilient to different kinds of irradiation due to the naturally developed protective mechanisms and compounds such as pigments. On the other hand, reasoned tissue engineering using plasma remains a critical task and requires very precise control of plasma parameters in order to mitigate its potential detrimental effects. Here we isolated a natural protective agent, microbially produced undecylprodigiosin ((5'2)-4'-methoxy-5'-[(5-undecy1-1H-pyrrol2-yl)methylenel-1H,5'H-2,2'-bipyrrole), and investigated its effects on human blood cells independently and in combination with plasma. Two apprOaches were applied; the first, undecylprodigiosin (UP pigment) was added to the blood cultures, which then were exposed to plasma (pre-treatment); and the second- the blood cultures were exposed to plasma and then treated with pigment (post-treatment). The interactions of plasma and UP pigment with blood cells were investigated by conducting a series of biological tests providing the information regarding their genotoxicity, cytotoxicity and redox modulating activities. The exposure of cells to plasma induced oxidative stress as well as certain genotoxic and cytotoxic effects seen as elevated micronuclei incidence, decreased cell proliferation and enhanced apoptosis. In blood cultures treated with UP pigment alone, we found that both cytotoxic and protective effects could be induced depending on the concentration used. The highest UP pigment concentration increased lipid peroxidation and the incidence of micronuclei by more than 70% with maximal suppression of cell proliferation. On the contrary, we found that the lowest UP pigment concentration displayed protective effects. In combined treatments with plasma and UP pigment, we found that UP pigment could provide spatial shielding to plasma exposure. In the pre-treatment approach, the incidence of micronuclei was reduced by 35.52% compared to control while malondialdehyde level decreased by 36% indicating a significant mitigation of membrane damage induced by plasma. These results open perspectives for utilizing UP pigment for protection against overexposures in the field of plasma medicine. (C) 2016 Elsevier GmbH. All rights reserved.",
publisher = "Elsevier Gmbh, Urban & Fischer Verlag, Jena",
journal = "Experimental and Toxicologic Pathology",
title = "Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro",
volume = "69",
number = "1",
pages = "55-62",
doi = "10.1016/j.etp.2016.11.003",
url = "Kon_3189"
}
Lazovic, S., Leskovac, A., Petrović, S., Šenerović, L., Krivokapic, N., Mitrovic, T., Bozovic, N., Vasic, V.,& Nikodinović-Runić, J.. (2017). Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro. in Experimental and Toxicologic Pathology
Elsevier Gmbh, Urban & Fischer Verlag, Jena., 69(1), 55-62.
https://doi.org/10.1016/j.etp.2016.11.003
Kon_3189
Lazovic S, Leskovac A, Petrović S, Šenerović L, Krivokapic N, Mitrovic T, Bozovic N, Vasic V, Nikodinović-Runić J. Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro. in Experimental and Toxicologic Pathology. 2017;69(1):55-62.
doi:10.1016/j.etp.2016.11.003
Kon_3189 .
Lazovic, Sasa, Leskovac, Andreja, Petrović, Sandra, Šenerović, Lidija, Krivokapic, Nevena, Mitrovic, Tatjana, Bozovic, Nikola, Vasic, Vesna, Nikodinović-Runić, Jasmina, "Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro" in Experimental and Toxicologic Pathology, 69, no. 1 (2017):55-62,
https://doi.org/10.1016/j.etp.2016.11.003 .,
Kon_3189 .
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Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine

Vujačić, Ana V.

(Универзитет у Београду, Хемијски факултет, 2013)

TY  - THES
AU  - Vujačić, Ana V.
PY  - 2013
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=238
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:5507/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=43575567
UR  - http://nardus.mpn.gov.rs/123456789/3459
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2603
AB  - Primenom više eksperimentalnih metoda (TEM, UV-Vis spektrofotometrija,fluorescentna spektroskopija, FTIR, DLS, merenja zeta potencijala) ispitane sunanočestice zlata različitih svojstava i veličina sa adsorbovanim boratnim (C6 i C9,5) icitratnim (C17 i C30) jonima na površini, u odsustvu i prisustvu TC boje (natrijum-(Z)-3-(5-hlor-2-((5-hlor-3-(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil)benzotiazol-3-ium-3-il)propan-1-sulfonata) u vodenoj sredini, i potvrđena je adsorpcija TC na površiniovih nanočestica. Merenje fluorescencije agregata čestica-boja, korigovane za efekatunutrašnjeg filtera, je ukazalo da nanočestice zlata, u zavisnosti od koncentracije, gasefluorescenciju TC boje. Nađeno je da je ovaj proces kvantitativno povezan sa stepenompokrivenosti površine nanočestica zlata molekulima TC boje. Pritom je efikasnostgašenja rasla sa povećanjem veličine čestica, pri čemu je koncentracija nanočestica zlatau rastvoru održavana konstantnom. Uz pretpostavku da je maksimalno gašenjefluorescencije TC boje ograničeno na potpunu monoslojnu pokrivenost površinenanočestica TC bojom (zavisno od orijentacije boje), eksperimentalno dobijene vrednostikoncentracije nanočestica C17 i C30 potrebne za potpuno gašenje fluorescencije TC bojesu bile niže od teorijski izračunatih, dok su za gašenje fluorecencije TC boje prikonstantnoj koncentraciji nanočestica dobijene više eksperimentalne vrednosti upoređenju sa teorijski izračunatim, iz čega je zaključeno da je najverovatnija orijentacijamolekula TC boje na površini ovih nanočestica kosa. S druge strane, u slučajunanočestica C6 i C9,5 teorijski dobijene vrednosti za koncentraciju TC boje potrebnu dapokrije površinu nanočestice i da fluorescencija boje bude potpuno ugašena, u slučaju svetri orijentacije, su niže u poređenju sa dobijenim eksperimentalnim vrednostima.Koncentracija nanočestica C9,5, potrebna da bi došlo do potpunog gašenja fluorescencijeTC boje, po vrednosti najpribližnije odgovara vertikalnoj orijentaciji boje duž kraćestrane, dok je u slučaju C6 eksperimentalno dobijen rezultat dosta niži od teorijskiizračunatih vrednosti za sve tri moguće orijentacije boje, iz čega je zaključeno da je napovršini ovih nanočestica boja smeštena u više od jednog sloja. Iz eksperimenata ukojima je ispitivano gašenja fluorescencije, izračunate su i konstante ravnoteže za procesadsorpcije TC na površini svih ispitivanih nanočestica...
AB  - The borate (C6 and C9,5) and citrate (C17 and C30) capped gold nanoparticles ofdifferent average core sizes and properties, were characterized by transmission electronmicroscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), fluorescencespectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering(DLS) and zeta potential measurements, in the absence and presence of cyanine dye,sodium (Z)-3-(5-chloro-2-((5-chloro-3-(3-sulfonatopropyl) benzothiazol-2(3H)-ylidene)methyl)benzothiazol-3-ium-3-yl)propane-1-sulfonate (TC) in water conditions,and the obtained results confirmed that TC was adsorbed on the surface of thesenanoparticles. The measurements of fluorescence of the particle–dye assembly, correctedfor inner filter effects, clearly indicated that the fluorescence of TC was quenched bygold nanoparticles on the concentration dependent manner. This process was found to bequantitatively related to the surface coverage of the Au nanoparticle by TC dyemolecules. Significant increase of quenching efficiency was noticed when nanoparticlesize increased, keeping the concentration of nanoparticles of different size constant. Theexperimental results of fluorescence quenching were compared with those obtained bytheoretical calculations, in which we assumed that the maximum quenching of TC dyefluorescence was restricted to full monolayer coverage of TC on the nanoparticlesurface. In case of C17 and C30 nanoparticles, the experimentally obtained values fornanoparticle concentration needed to completely quench TC dye fluorescence werelower than the calculated ones, while higher experimental values in comparision withcalculated ones of quenched TC dye at constant nanoparticle concentration wereobtained. These findings leaded to the conclusion that the most probable orientation ofTC dye molecules on the surface of these nanoparticle was slanted. On the other hand, incase of C6 and C9,5 nanoparticles, the obtained calculated values for TC concentrationneeded to cover the nanoparticle surface and be completely quenched, for all threepossible orientations of TC dye, were lower in comparision with the experimental values.The experimentally obtained value of C9,5 concentration needed to completely quenchTC dye fluorescence most closely corresponds to vertical TC dye orientation along theshort side, while the experimentally obtained results in case of C6 nanoparticles weremuch lower than theoretically calculated values for all three possible TC dye orientations.These findings indicated that on the surface of C6 nanoparticles the dye wasaccommodated in more than one layer. In addition, from the fluorescence quenchingexperiments, the equilibrium constants for the sorption of TC on the surface of allmentioned nanoparticles were calculated...
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine
T1  - Kinetics and mechanism of sodium (Z)-3-(5-chloro-2-((5-chloro-3-(3-sulfonatopropyl) benzothiazol-2(3H)-ylidene)methyl)benzo- thiazol-3-ium-3-yl)propane-1-sulfonate adsorption on gold nanoparticle colloids of different properties and size
ER  - 
@phdthesis{
author = "Vujačić, Ana V.",
year = "2013",
abstract = "Primenom više eksperimentalnih metoda (TEM, UV-Vis spektrofotometrija,fluorescentna spektroskopija, FTIR, DLS, merenja zeta potencijala) ispitane sunanočestice zlata različitih svojstava i veličina sa adsorbovanim boratnim (C6 i C9,5) icitratnim (C17 i C30) jonima na površini, u odsustvu i prisustvu TC boje (natrijum-(Z)-3-(5-hlor-2-((5-hlor-3-(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil)benzotiazol-3-ium-3-il)propan-1-sulfonata) u vodenoj sredini, i potvrđena je adsorpcija TC na površiniovih nanočestica. Merenje fluorescencije agregata čestica-boja, korigovane za efekatunutrašnjeg filtera, je ukazalo da nanočestice zlata, u zavisnosti od koncentracije, gasefluorescenciju TC boje. Nađeno je da je ovaj proces kvantitativno povezan sa stepenompokrivenosti površine nanočestica zlata molekulima TC boje. Pritom je efikasnostgašenja rasla sa povećanjem veličine čestica, pri čemu je koncentracija nanočestica zlatau rastvoru održavana konstantnom. Uz pretpostavku da je maksimalno gašenjefluorescencije TC boje ograničeno na potpunu monoslojnu pokrivenost površinenanočestica TC bojom (zavisno od orijentacije boje), eksperimentalno dobijene vrednostikoncentracije nanočestica C17 i C30 potrebne za potpuno gašenje fluorescencije TC bojesu bile niže od teorijski izračunatih, dok su za gašenje fluorecencije TC boje prikonstantnoj koncentraciji nanočestica dobijene više eksperimentalne vrednosti upoređenju sa teorijski izračunatim, iz čega je zaključeno da je najverovatnija orijentacijamolekula TC boje na površini ovih nanočestica kosa. S druge strane, u slučajunanočestica C6 i C9,5 teorijski dobijene vrednosti za koncentraciju TC boje potrebnu dapokrije površinu nanočestice i da fluorescencija boje bude potpuno ugašena, u slučaju svetri orijentacije, su niže u poređenju sa dobijenim eksperimentalnim vrednostima.Koncentracija nanočestica C9,5, potrebna da bi došlo do potpunog gašenja fluorescencijeTC boje, po vrednosti najpribližnije odgovara vertikalnoj orijentaciji boje duž kraćestrane, dok je u slučaju C6 eksperimentalno dobijen rezultat dosta niži od teorijskiizračunatih vrednosti za sve tri moguće orijentacije boje, iz čega je zaključeno da je napovršini ovih nanočestica boja smeštena u više od jednog sloja. Iz eksperimenata ukojima je ispitivano gašenja fluorescencije, izračunate su i konstante ravnoteže za procesadsorpcije TC na površini svih ispitivanih nanočestica..., The borate (C6 and C9,5) and citrate (C17 and C30) capped gold nanoparticles ofdifferent average core sizes and properties, were characterized by transmission electronmicroscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), fluorescencespectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering(DLS) and zeta potential measurements, in the absence and presence of cyanine dye,sodium (Z)-3-(5-chloro-2-((5-chloro-3-(3-sulfonatopropyl) benzothiazol-2(3H)-ylidene)methyl)benzothiazol-3-ium-3-yl)propane-1-sulfonate (TC) in water conditions,and the obtained results confirmed that TC was adsorbed on the surface of thesenanoparticles. The measurements of fluorescence of the particle–dye assembly, correctedfor inner filter effects, clearly indicated that the fluorescence of TC was quenched bygold nanoparticles on the concentration dependent manner. This process was found to bequantitatively related to the surface coverage of the Au nanoparticle by TC dyemolecules. Significant increase of quenching efficiency was noticed when nanoparticlesize increased, keeping the concentration of nanoparticles of different size constant. Theexperimental results of fluorescence quenching were compared with those obtained bytheoretical calculations, in which we assumed that the maximum quenching of TC dyefluorescence was restricted to full monolayer coverage of TC on the nanoparticlesurface. In case of C17 and C30 nanoparticles, the experimentally obtained values fornanoparticle concentration needed to completely quench TC dye fluorescence werelower than the calculated ones, while higher experimental values in comparision withcalculated ones of quenched TC dye at constant nanoparticle concentration wereobtained. These findings leaded to the conclusion that the most probable orientation ofTC dye molecules on the surface of these nanoparticle was slanted. On the other hand, incase of C6 and C9,5 nanoparticles, the obtained calculated values for TC concentrationneeded to cover the nanoparticle surface and be completely quenched, for all threepossible orientations of TC dye, were lower in comparision with the experimental values.The experimentally obtained value of C9,5 concentration needed to completely quenchTC dye fluorescence most closely corresponds to vertical TC dye orientation along theshort side, while the experimentally obtained results in case of C6 nanoparticles weremuch lower than theoretically calculated values for all three possible TC dye orientations.These findings indicated that on the surface of C6 nanoparticles the dye wasaccommodated in more than one layer. In addition, from the fluorescence quenchingexperiments, the equilibrium constants for the sorption of TC on the surface of allmentioned nanoparticles were calculated...",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine, Kinetics and mechanism of sodium (Z)-3-(5-chloro-2-((5-chloro-3-(3-sulfonatopropyl) benzothiazol-2(3H)-ylidene)methyl)benzo- thiazol-3-ium-3-yl)propane-1-sulfonate adsorption on gold nanoparticle colloids of different properties and size"
}
Vujačić, A. V.. (2013). Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
Vujačić AV. Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine. in Универзитет у Београду. 2013;..
Vujačić, Ana V., "Kinetika i mehanizam adsorpcije natrijum (Z)-3-(5-hlor-2-((5-hlor-3(3-sulfonatopropil)benzotiazol-2(3H)-iliden)metil )ben zotiazol-3-ium-3-il)propan-1-sulfonata na koloidne čestice zlata različitih svojstava i veličine" in Универзитет у Београду (2013).

Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom

Petrović, Voin

(Универзитет у Београду, Хемијски факултет, 2013)

TY  - THES
AU  - Petrović, Voin
PY  - 2013
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=3890
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:13062/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=44723215
UR  - http://nardus.mpn.gov.rs/123456789/6544
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2707
AB  - Na+/K+ ATPaza je membranski enzim koji koristi energiju oslobođenu iz molekulaadenozin trifosfata da bi regulisao odnos koncentracije jona kalijuma i natrijuma sa obestrane ćelijske membrane većine živih bića. Pored transporterske uloge, on obavlja ifunkciju signalnog molekula, jer je uključen u regulaciju aktivnosti Src kinaze, koja je daljeuključena u signalne puteve unutar ćelije i reguliše preživljavanje ćelije. Zbog ovoihsvojstava Na+/K+ ATPaza je prepoznata kao važna terapeutska meta u velikom brojurazličitih patogenih stanja uključujući i tumore. Kompleksi plemenitih metala, a naročitozlata predstavljaju novu veliku grupu jedinjenja koja pokazuje sposobnost inhibicije Na+/K+ATPaze. Ovo ih čini potencijalnim terapeuticima, analognim kompleksima platine koji su usastavu modernih hemoterapija. Osim kompleksnih jedinjenja zlata, interesantna svojstvapokazuju i nanočestice zlata. U ovoj studiji ispitivani su efekti 9 kompleksnih jedinjenjazlata i 3 tipa koloidnih nanočestica zlata na različite preparate enzima Na+/K+ ATPaze.Dobijeni rezultati ukazuju na to da 6 od 9 ispitivanih kompleksa ima umereno jakinhibitorni uticaj na Na+/K+ ATPazu. Pored toga, pokazano je da je reč o nekompetitivnojreverzibilnoj inhibiciji, koja se može otkloniti dodatkom donora –SH grupe kao što sucistein i glutation. Osim toga, inhibicija se može i u potpunosti preduprediti istim ovimsupstancijama. Stoga je zaključeno da se vezivanje kompleksa za enzim odvija preko –SHostataka cisteina u enzimu. Pokazano je da neki od ispitivanih kompleksa imaju izuzetnojak citostatski efekat, što ih čini dobrim kandidatima za dalje medicinske studije.Upotrebom MALDI TOF masene spektrometrije pokazano je da postoji direktna reakcijaizmeđu kompleksa i donora –SH grupe, tj da ove dve vrste direktno reaguju kada suprisutne u rastvoru.Nanočestice zlata koje su ispitivane nisu dale zapažen inhibitorni efekat. Tip nanočesticaobeležen kao C3 koji sadrži nanočestice zlata prečnika 9,5 nm, pokazao je neobičnasvojstva - dodatkom u preparat sinaptozomalnih plazma membrana, doveo je do porastaaktivnosti Na+/K+ ATPaze u tom preparatu dvostruko, dok se aktivnost ostalih prisutnihenzima nije menjala. Ispitivanjem ove interakcije pokazano je da je u pitanju fizičkapromena u preparatu do koje dolazi usled dva tipa hemijske interakcije između koloida ipreparata enzima. Uočene su promene u UV-vis i FTIR spektrima koloida po dodatkuenzima, a upotrebom atomske mikroskopije uočeno je da dolazi do promena unanostrukturi preparata enzima koje izaziva povećanje aktivne površine ćelijske membrane,te tako veći broj molekula enzima postaje dostupan za reakciju i javlja se porast aktivnostienzima u preparatu. Selektivnost enzima za njegove prirodne ligande ostaje neizmenjena, adobijeni preparat pojačane aktivnosti stabilan je najmanje sat vremena.Zaključeno je da ispitivani kompleksi zlata mogu da budu od značaja za dalji razvojantitumorskih terapija, kao i da koloidne nanočestice zlata mogu poslužiti za razvojosetljivijih testova za merenje aktivnosti membranskih enzima.
AB  - Na+/K+ ATPase is a membrane enzyme that uses the enegry released from the molecule ofadenosine triphosphate to regulate the sodium and potasium ion concentration on either sideof the cell membrane in most living creatures. Appart from its transporter role, it also has arole as a signal molecule, because it regulates the activity of Src kinase, an importantenzyme in cell signaling and survival. Beacuse of these properties, Na+/K+ ATPase isrecognized as an important molecular target in many disorders including tumors. Noblemetal complexes, and especially gold complexes have shown the tendency to inhibitNa+/K+ ATPase. This makes them potential terapeutics, analogous to platinum basedcomplexes that are a part of modern chemotherapy. Colloid nanoparticles of gold have alsoshown interesting properties in the past. This study presents the findings on the interactionof several preparations of Na+/K+ ATPase with 9 different complexes of gold and 3different types of gold colloid nanoparticles.Results shown in this thesis indicate that 6 out of 9 investigated complexes have amoderatley strong inhibitory effect upon the Na+/K+ ATPase. It is shown that this inhibitionis noncompetitive and reversible, and that it can be reversed by –SH group donors such ascysteine and glutathione. Moreover, this inhibition can be fully prevented by adding thesesubstances prior to the addition of the complex. Therefore it is concluded that the bindingof these complexes takes place through –SH groups of cysteine residues in the enzyme.Some of the investigated complexes have shown a strong cytotoxic effect upon humanlymphocytes, which makes them good candidates for further clinical studies. MALDI TOFmass spectroscopy has shown that there is a direct reaction between –SH group donors andthe gold complex.Investigated nanoparticles yielded no significant inhibitory effect. One type of thenanoparticles, however, has shown some very unusual properties. Upon the addition of thistype of colloid nanoparticles, labeled C3 and with an average diameter of 9.5 nm, to thepreparation of synaptosomal plasma membranes, the activity of Na+/K+ ATPase doubled,while the activity of other present enzymes remained the same. Further investigation of thisinteraction has shown that the cause of this is a physical change in the structure of themembrane fragments. It is the result of two paralel chemical interactions that take placewhen the nanoparticles are added to the enzyme preparation. Changes in UV/vis and FTIRspectra of the nanoparticles were observed and using atomic force microscopy it waspossible to visualize the change in the nanostructure of the enzyme preparation upon theaddition of nanoparticles. This change resulted in an increase of the active membranesurface, exposing more molecules of the enzyme and making them available for thereaction. This caused an increase of the enzyme activity. Selectivity of the Na+/K+ ATPasetowards its natural ligands was preserved, and the effect of increased activity persisted forat least an hour before diminishing.In conclusion, investigated complexes and nanoparticles of gold have shown importantproperties. The effects of gold complexes make them potential antitumor drugs, while thenanoparticles of gold may be used to develop better assays for membrane enzymes.
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom
T1  - Investigation of in vitro interactions of gold compounds with Na+/K+ ATPase
ER  - 
@phdthesis{
author = "Petrović, Voin",
year = "2013",
abstract = "Na+/K+ ATPaza je membranski enzim koji koristi energiju oslobođenu iz molekulaadenozin trifosfata da bi regulisao odnos koncentracije jona kalijuma i natrijuma sa obestrane ćelijske membrane većine živih bića. Pored transporterske uloge, on obavlja ifunkciju signalnog molekula, jer je uključen u regulaciju aktivnosti Src kinaze, koja je daljeuključena u signalne puteve unutar ćelije i reguliše preživljavanje ćelije. Zbog ovoihsvojstava Na+/K+ ATPaza je prepoznata kao važna terapeutska meta u velikom brojurazličitih patogenih stanja uključujući i tumore. Kompleksi plemenitih metala, a naročitozlata predstavljaju novu veliku grupu jedinjenja koja pokazuje sposobnost inhibicije Na+/K+ATPaze. Ovo ih čini potencijalnim terapeuticima, analognim kompleksima platine koji su usastavu modernih hemoterapija. Osim kompleksnih jedinjenja zlata, interesantna svojstvapokazuju i nanočestice zlata. U ovoj studiji ispitivani su efekti 9 kompleksnih jedinjenjazlata i 3 tipa koloidnih nanočestica zlata na različite preparate enzima Na+/K+ ATPaze.Dobijeni rezultati ukazuju na to da 6 od 9 ispitivanih kompleksa ima umereno jakinhibitorni uticaj na Na+/K+ ATPazu. Pored toga, pokazano je da je reč o nekompetitivnojreverzibilnoj inhibiciji, koja se može otkloniti dodatkom donora –SH grupe kao što sucistein i glutation. Osim toga, inhibicija se može i u potpunosti preduprediti istim ovimsupstancijama. Stoga je zaključeno da se vezivanje kompleksa za enzim odvija preko –SHostataka cisteina u enzimu. Pokazano je da neki od ispitivanih kompleksa imaju izuzetnojak citostatski efekat, što ih čini dobrim kandidatima za dalje medicinske studije.Upotrebom MALDI TOF masene spektrometrije pokazano je da postoji direktna reakcijaizmeđu kompleksa i donora –SH grupe, tj da ove dve vrste direktno reaguju kada suprisutne u rastvoru.Nanočestice zlata koje su ispitivane nisu dale zapažen inhibitorni efekat. Tip nanočesticaobeležen kao C3 koji sadrži nanočestice zlata prečnika 9,5 nm, pokazao je neobičnasvojstva - dodatkom u preparat sinaptozomalnih plazma membrana, doveo je do porastaaktivnosti Na+/K+ ATPaze u tom preparatu dvostruko, dok se aktivnost ostalih prisutnihenzima nije menjala. Ispitivanjem ove interakcije pokazano je da je u pitanju fizičkapromena u preparatu do koje dolazi usled dva tipa hemijske interakcije između koloida ipreparata enzima. Uočene su promene u UV-vis i FTIR spektrima koloida po dodatkuenzima, a upotrebom atomske mikroskopije uočeno je da dolazi do promena unanostrukturi preparata enzima koje izaziva povećanje aktivne površine ćelijske membrane,te tako veći broj molekula enzima postaje dostupan za reakciju i javlja se porast aktivnostienzima u preparatu. Selektivnost enzima za njegove prirodne ligande ostaje neizmenjena, adobijeni preparat pojačane aktivnosti stabilan je najmanje sat vremena.Zaključeno je da ispitivani kompleksi zlata mogu da budu od značaja za dalji razvojantitumorskih terapija, kao i da koloidne nanočestice zlata mogu poslužiti za razvojosetljivijih testova za merenje aktivnosti membranskih enzima., Na+/K+ ATPase is a membrane enzyme that uses the enegry released from the molecule ofadenosine triphosphate to regulate the sodium and potasium ion concentration on either sideof the cell membrane in most living creatures. Appart from its transporter role, it also has arole as a signal molecule, because it regulates the activity of Src kinase, an importantenzyme in cell signaling and survival. Beacuse of these properties, Na+/K+ ATPase isrecognized as an important molecular target in many disorders including tumors. Noblemetal complexes, and especially gold complexes have shown the tendency to inhibitNa+/K+ ATPase. This makes them potential terapeutics, analogous to platinum basedcomplexes that are a part of modern chemotherapy. Colloid nanoparticles of gold have alsoshown interesting properties in the past. This study presents the findings on the interactionof several preparations of Na+/K+ ATPase with 9 different complexes of gold and 3different types of gold colloid nanoparticles.Results shown in this thesis indicate that 6 out of 9 investigated complexes have amoderatley strong inhibitory effect upon the Na+/K+ ATPase. It is shown that this inhibitionis noncompetitive and reversible, and that it can be reversed by –SH group donors such ascysteine and glutathione. Moreover, this inhibition can be fully prevented by adding thesesubstances prior to the addition of the complex. Therefore it is concluded that the bindingof these complexes takes place through –SH groups of cysteine residues in the enzyme.Some of the investigated complexes have shown a strong cytotoxic effect upon humanlymphocytes, which makes them good candidates for further clinical studies. MALDI TOFmass spectroscopy has shown that there is a direct reaction between –SH group donors andthe gold complex.Investigated nanoparticles yielded no significant inhibitory effect. One type of thenanoparticles, however, has shown some very unusual properties. Upon the addition of thistype of colloid nanoparticles, labeled C3 and with an average diameter of 9.5 nm, to thepreparation of synaptosomal plasma membranes, the activity of Na+/K+ ATPase doubled,while the activity of other present enzymes remained the same. Further investigation of thisinteraction has shown that the cause of this is a physical change in the structure of themembrane fragments. It is the result of two paralel chemical interactions that take placewhen the nanoparticles are added to the enzyme preparation. Changes in UV/vis and FTIRspectra of the nanoparticles were observed and using atomic force microscopy it waspossible to visualize the change in the nanostructure of the enzyme preparation upon theaddition of nanoparticles. This change resulted in an increase of the active membranesurface, exposing more molecules of the enzyme and making them available for thereaction. This caused an increase of the enzyme activity. Selectivity of the Na+/K+ ATPasetowards its natural ligands was preserved, and the effect of increased activity persisted forat least an hour before diminishing.In conclusion, investigated complexes and nanoparticles of gold have shown importantproperties. The effects of gold complexes make them potential antitumor drugs, while thenanoparticles of gold may be used to develop better assays for membrane enzymes.",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom, Investigation of in vitro interactions of gold compounds with Na+/K+ ATPase"
}
Petrović, V.. (2013). Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
Petrović V. Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom. in Универзитет у Београду. 2013;..
Petrović, Voin, "Ispitivanje in vitro interakcija jedinjenja zlata sa Na+/K+ ATPazom" in Универзитет у Београду (2013).

Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze

Lazarević-Pašti, Tamara

(Универзитет у Београду, Хемијски факултет, 2012)

TY  - THES
AU  - Lazarević-Pašti, Tamara
PY  - 2012
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=332
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:5873/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=41104655
UR  - http://nardus.mpn.gov.rs/123456789/3468
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2612
AB  - Ispitana je inhibicija slobodne acetilholinesteraze (AChE) odabranim organotiofosfatima (OP) (diazinon, malation, hlorpirifos, azinfos-metil, forat) i njihovim oksoanalozima (diazokson, malaokson, hlorpirifos-okson, azinfos-metil-okson, forat-okson), pri čemu su optimizovani uslovi za detekciju najniže koncentracije tih jedinjenja primenom AChE testa. Određene su IC50 vrednosti za sva navedena jedinjenja. U cilju povećanja osetljivosti AChE testa, ispitivani organo-tiofosfati prevedeni su u okso-analoge u prisustvu enzima mijeloperoksidaze (MPO). To je potvreno pomoćuUPLC i GC/MS analize. Nastali oksidacioni proizvodi stabilni su najmanje 1h. Maksimalne koncentracije oksona dobijaju se kada se organo-tiofosfati inkubiraju sa 100 nM MPO u prisustvu H2O2 koncentracije 50 μM, pri pH 6, na temperaturi 25 °C u toku 10 minuta. Oksidacija OP u prisustvu MPO pod navedenim uslovima primenjena je u modifikaciji metode za detekciju OP na bazi inhibicije AChE. Određena je granica detekcije modifikovane metode, kao i efikasnost oksidacije i njena primena na smešu OP. Gore navedeni organo-tiofosfati prevedeni su u odgovarajue oksone i pomoću elektrohemijski generisanih halogena. Proizvodi koji nastaju identifikovani su kao oksoni pomoću UPLC analize. Utvrđeno je da je najefikasnija oksidacija elektrogenerisanim bromom u toku 15 minuta. Određena je i granica detekcije AChE testa za odreivanje OP kada su OP oksidovani elektrohemijski generisanim bromom...
AB  - The inhibition of acetylcholinesterase in the presence of selected organothiophosphates (diazinon, malathion, chlorpyrifos, azinphos-methyl, phorate) andtheir oxo-analogues (diazoxon, malaoxon, chlorpyrifos-oxon, azinphos-methyl-oxon,phorate-oxon) was examined. Experimental conditions were optimized to detect the lowestposible concentrations of these compounds using AChE test. IC50 values were determinedfor all the mentioned compounds.Investigated organothiophosphates have been converted into their oxo-analogues inthe presence of the enzyme myeloperoxidase. Oxidation products were detected usingUPLC and GC/MS analysis. It was found that the products are stable within minimum 1h.In order to optimize oxidation procedure and achieve maximum concentrations of oxons,the optimal concentrations of H2O2 (50 μM) and MPO (100 nM) were determined. Also,the optimal incubation time of OPs and MPO (10 min), as well as the optimal pH (6) andtemperature (25 °C) were estimated. Oxidation of OPs in the presence of MPO underoptimal conditions was applied as a modification of the method for detecting OP usingAChE test. The detection limits were determined for the modified method, as well as theefficiency of oxidation and its application for the analysi of sintetic mixture of OPs.Examined organothiophosphates have been converted into their oxo-forms usingelectrochemically generated halogens. Products have been identified as oxons using UPLCanalysis. It was found that the the most efficient oxidation of OPs was carried out by after15 minutes of oxidation with electrogenerated bromine. Detection limits were determined,too.
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze
T1  - Application of organothiophosphate pesticides oxidation in methods for their detection based on acetylcholinesterase inhibition
ER  - 
@phdthesis{
author = "Lazarević-Pašti, Tamara",
year = "2012",
abstract = "Ispitana je inhibicija slobodne acetilholinesteraze (AChE) odabranim organotiofosfatima (OP) (diazinon, malation, hlorpirifos, azinfos-metil, forat) i njihovim oksoanalozima (diazokson, malaokson, hlorpirifos-okson, azinfos-metil-okson, forat-okson), pri čemu su optimizovani uslovi za detekciju najniže koncentracije tih jedinjenja primenom AChE testa. Određene su IC50 vrednosti za sva navedena jedinjenja. U cilju povećanja osetljivosti AChE testa, ispitivani organo-tiofosfati prevedeni su u okso-analoge u prisustvu enzima mijeloperoksidaze (MPO). To je potvreno pomoćuUPLC i GC/MS analize. Nastali oksidacioni proizvodi stabilni su najmanje 1h. Maksimalne koncentracije oksona dobijaju se kada se organo-tiofosfati inkubiraju sa 100 nM MPO u prisustvu H2O2 koncentracije 50 μM, pri pH 6, na temperaturi 25 °C u toku 10 minuta. Oksidacija OP u prisustvu MPO pod navedenim uslovima primenjena je u modifikaciji metode za detekciju OP na bazi inhibicije AChE. Određena je granica detekcije modifikovane metode, kao i efikasnost oksidacije i njena primena na smešu OP. Gore navedeni organo-tiofosfati prevedeni su u odgovarajue oksone i pomoću elektrohemijski generisanih halogena. Proizvodi koji nastaju identifikovani su kao oksoni pomoću UPLC analize. Utvrđeno je da je najefikasnija oksidacija elektrogenerisanim bromom u toku 15 minuta. Određena je i granica detekcije AChE testa za odreivanje OP kada su OP oksidovani elektrohemijski generisanim bromom..., The inhibition of acetylcholinesterase in the presence of selected organothiophosphates (diazinon, malathion, chlorpyrifos, azinphos-methyl, phorate) andtheir oxo-analogues (diazoxon, malaoxon, chlorpyrifos-oxon, azinphos-methyl-oxon,phorate-oxon) was examined. Experimental conditions were optimized to detect the lowestposible concentrations of these compounds using AChE test. IC50 values were determinedfor all the mentioned compounds.Investigated organothiophosphates have been converted into their oxo-analogues inthe presence of the enzyme myeloperoxidase. Oxidation products were detected usingUPLC and GC/MS analysis. It was found that the products are stable within minimum 1h.In order to optimize oxidation procedure and achieve maximum concentrations of oxons,the optimal concentrations of H2O2 (50 μM) and MPO (100 nM) were determined. Also,the optimal incubation time of OPs and MPO (10 min), as well as the optimal pH (6) andtemperature (25 °C) were estimated. Oxidation of OPs in the presence of MPO underoptimal conditions was applied as a modification of the method for detecting OP usingAChE test. The detection limits were determined for the modified method, as well as theefficiency of oxidation and its application for the analysi of sintetic mixture of OPs.Examined organothiophosphates have been converted into their oxo-forms usingelectrochemically generated halogens. Products have been identified as oxons using UPLCanalysis. It was found that the the most efficient oxidation of OPs was carried out by after15 minutes of oxidation with electrogenerated bromine. Detection limits were determined,too.",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze, Application of organothiophosphate pesticides oxidation in methods for their detection based on acetylcholinesterase inhibition"
}
Lazarević-Pašti, T.. (2012). Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
Lazarević-Pašti T. Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze. in Универзитет у Београду. 2012;..
Lazarević-Pašti, Tamara, "Primena oksidacije organo-tiofosfatnih pesticida u metodama za njihovu detekciju na bazi inhibicije acetilholinesteraze" in Универзитет у Београду (2012).