TY  - JOUR
AU  - Srbljanović, Jelena
AU  - Bobić, Branko
AU  - Štajner, Tijana
AU  - Uzelac, Aleksandra
AU  - Opsenica, Igor
AU  - Terzić-Jovanović, Nataša
AU  - Bauman, Neda
AU  - Šolaja, Bogdan
AU  - Đurković-Đaković, Olgica
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3721
AB  - Objectives: Malaria treatment is impeded by increasing resistance to conventional antimalarial drugs. Here we explored the activity of ten novel benzothiophene, thiophene and benzene aminoquinolines. Methods: In vitro testing was performed by the lactate dehydrogenase assay in chloroquine (CQ)-sensitive Plasmodium falciparum strain 3D7 and CQ-resistant (CQR) P. falciparum strain Dd2. In vivo activity was evaluated by a modified Thompson test using C57BL/6 mice infected with Plasmodium berghei ANKA strain. Results: Nine of the ten compounds had a lower 50% inhibitory concentration (IC50) than CQ against the CQR strain Dd2. Five of these compounds that were available for in vivo evaluation were shown to be non-toxic. All five compounds administered at a dose of 160 mg/kg/day for 3 days prolonged the survival of treated compared with untreated mice. Untreated control mice died by Day 7 with a mean parasitaemia of 15%. Among treated mice, a dichotomous outcome was observed, with a two-third majority of treated mice dying by Day 17 with a low mean parasitaemia of 5%, whilst one-third survived longer with a mean hyperparasitaemia of 70%; specifically, five of these mice survived a mean of 25 days, whilst two even survived past Day 31. Conclusions: The significant antimalarial potential of this aminoquinoline series is illustrated by its excellent in vitro activity against the CQR P. falciparum strain and significant in vivo activity. Interestingly, compounds ClAQ7, ClAQ9 and ClAQ11 were able to confer resistance to cerebral malaria and afford a switch to hyperparasitaemia to mice prone to the neurological syndrome.
PB  - Elsevier
T2  - Journal of Global Antimicrobial Resistance
T1  - Aminoquinolines afford resistance to cerebral malaria in susceptible mice
VL  - 23
SP  - 20
EP  - 25
DO  - 10.1016/j.jgar.2020.07.027
ER  - 

@article{
author = "Srbljanović, Jelena and Bobić, Branko and Štajner, Tijana and Uzelac, Aleksandra and Opsenica, Igor and Terzić-Jovanović, Nataša and Bauman, Neda and Šolaja, Bogdan and Đurković-Đaković, Olgica",
year = "2020",
abstract = "Objectives: Malaria treatment is impeded by increasing resistance to conventional antimalarial drugs. Here we explored the activity of ten novel benzothiophene, thiophene and benzene aminoquinolines. Methods: In vitro testing was performed by the lactate dehydrogenase assay in chloroquine (CQ)-sensitive Plasmodium falciparum strain 3D7 and CQ-resistant (CQR) P. falciparum strain Dd2. In vivo activity was evaluated by a modified Thompson test using C57BL/6 mice infected with Plasmodium berghei ANKA strain. Results: Nine of the ten compounds had a lower 50% inhibitory concentration (IC50) than CQ against the CQR strain Dd2. Five of these compounds that were available for in vivo evaluation were shown to be non-toxic. All five compounds administered at a dose of 160 mg/kg/day for 3 days prolonged the survival of treated compared with untreated mice. Untreated control mice died by Day 7 with a mean parasitaemia of 15%. Among treated mice, a dichotomous outcome was observed, with a two-third majority of treated mice dying by Day 17 with a low mean parasitaemia of 5%, whilst one-third survived longer with a mean hyperparasitaemia of 70%; specifically, five of these mice survived a mean of 25 days, whilst two even survived past Day 31. Conclusions: The significant antimalarial potential of this aminoquinoline series is illustrated by its excellent in vitro activity against the CQR P. falciparum strain and significant in vivo activity. Interestingly, compounds ClAQ7, ClAQ9 and ClAQ11 were able to confer resistance to cerebral malaria and afford a switch to hyperparasitaemia to mice prone to the neurological syndrome.",
publisher = "Elsevier",
journal = "Journal of Global Antimicrobial Resistance",
title = "Aminoquinolines afford resistance to cerebral malaria in susceptible mice",
volume = "23",
pages = "20-25",
doi = "10.1016/j.jgar.2020.07.027"
}

Srbljanović, J., Bobić, B., Štajner, T., Uzelac, A., Opsenica, I., Terzić-Jovanović, N., Bauman, N., Šolaja, B.,& Đurković-Đaković, O.. (2020). Aminoquinolines afford resistance to cerebral malaria in susceptible mice. in Journal of Global Antimicrobial Resistance
Elsevier., 23, 20-25.
https://doi.org/10.1016/j.jgar.2020.07.027

Srbljanović J, Bobić B, Štajner T, Uzelac A, Opsenica I, Terzić-Jovanović N, Bauman N, Šolaja B, Đurković-Đaković O. Aminoquinolines afford resistance to cerebral malaria in susceptible mice. in Journal of Global Antimicrobial Resistance. 2020;23:20-25.
doi:10.1016/j.jgar.2020.07.027 .

Srbljanović, Jelena, Bobić, Branko, Štajner, Tijana, Uzelac, Aleksandra, Opsenica, Igor, Terzić-Jovanović, Nataša, Bauman, Neda, Šolaja, Bogdan, Đurković-Đaković, Olgica, "Aminoquinolines afford resistance to cerebral malaria in susceptible mice" in Journal of Global Antimicrobial Resistance, 23 (2020):20-25,
https://doi.org/10.1016/j.jgar.2020.07.027 . .

TY  - JOUR
AU  - Simić, Stefan
AU  - Jeremić, Sanja
AU  - Đokić, Lidija
AU  - Božić, Nataša
AU  - Vujčić, Zoran
AU  - Lončar, Nikola
AU  - Senthamaraikannan, Ramsankar
AU  - Babu, Ramesh Padamati
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3052
AB  - Biocatalytic oxidations mediated by laccases are gaining importance due to their versatility and beneficial environmental effects. In this study, the oxidation of 1,4-dihydropyridines has been performed using three different types of bacterial laccase-based catalysts: purified laccase from Bacillus licheniformis ATCC 9945a (BliLacc), Escherichia coli whole cells expressing this laccase, and bacterial nanocellulose (BNC) supported BliLacc catalysts. The catalysts based on bacterial laccase were compared to the commercially available Trametes versicolor laccase (TvLacc). The oxidation product of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate was obtained within 7–24 h with good yields (70–99%) with all three biocatalysts. The substrate scope was examined with five additional 1,4-dihydropyridines, one of which was oxidized in high yield. Whole-cell biocatalyst was stable when stored for up to 1-month at 4 °C. In addition, evidence has been provided that multicopper oxidase CueO from the E. coli expression host contributed to the oxidation efficiency of the whole-cell biocatalyst. The immobilized whole-cell biocatalyst showed satisfactory activity and retained 37% of its original activity after three biotransformation cycles.
PB  - Elsevier
T2  - Enzyme and Microbial Technology
T1  - Development of an efficient biocatalytic system based on bacterial laccase for the oxidation of selected 1,4-dihydropyridines
VL  - 132
SP  - 109411
DO  - 10.1016/j.enzmictec.2019.109411
ER  - 

@article{
author = "Simić, Stefan and Jeremić, Sanja and Đokić, Lidija and Božić, Nataša and Vujčić, Zoran and Lončar, Nikola and Senthamaraikannan, Ramsankar and Babu, Ramesh Padamati and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2020",
abstract = "Biocatalytic oxidations mediated by laccases are gaining importance due to their versatility and beneficial environmental effects. In this study, the oxidation of 1,4-dihydropyridines has been performed using three different types of bacterial laccase-based catalysts: purified laccase from Bacillus licheniformis ATCC 9945a (BliLacc), Escherichia coli whole cells expressing this laccase, and bacterial nanocellulose (BNC) supported BliLacc catalysts. The catalysts based on bacterial laccase were compared to the commercially available Trametes versicolor laccase (TvLacc). The oxidation product of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate was obtained within 7–24 h with good yields (70–99%) with all three biocatalysts. The substrate scope was examined with five additional 1,4-dihydropyridines, one of which was oxidized in high yield. Whole-cell biocatalyst was stable when stored for up to 1-month at 4 °C. In addition, evidence has been provided that multicopper oxidase CueO from the E. coli expression host contributed to the oxidation efficiency of the whole-cell biocatalyst. The immobilized whole-cell biocatalyst showed satisfactory activity and retained 37% of its original activity after three biotransformation cycles.",
publisher = "Elsevier",
journal = "Enzyme and Microbial Technology",
title = "Development of an efficient biocatalytic system based on bacterial laccase for the oxidation of selected 1,4-dihydropyridines",
volume = "132",
pages = "109411",
doi = "10.1016/j.enzmictec.2019.109411"
}

Simić, S., Jeremić, S., Đokić, L., Božić, N., Vujčić, Z., Lončar, N., Senthamaraikannan, R., Babu, R. P., Opsenica, I.,& Nikodinović-Runić, J.. (2020). Development of an efficient biocatalytic system based on bacterial laccase for the oxidation of selected 1,4-dihydropyridines. in Enzyme and Microbial Technology
Elsevier., 132, 109411.
https://doi.org/10.1016/j.enzmictec.2019.109411

Simić S, Jeremić S, Đokić L, Božić N, Vujčić Z, Lončar N, Senthamaraikannan R, Babu RP, Opsenica I, Nikodinović-Runić J. Development of an efficient biocatalytic system based on bacterial laccase for the oxidation of selected 1,4-dihydropyridines. in Enzyme and Microbial Technology. 2020;132:109411.
doi:10.1016/j.enzmictec.2019.109411 .

Simić, Stefan, Jeremić, Sanja, Đokić, Lidija, Božić, Nataša, Vujčić, Zoran, Lončar, Nikola, Senthamaraikannan, Ramsankar, Babu, Ramesh Padamati, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Development of an efficient biocatalytic system based on bacterial laccase for the oxidation of selected 1,4-dihydropyridines" in Enzyme and Microbial Technology, 132 (2020):109411,
https://doi.org/10.1016/j.enzmictec.2019.109411 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Simić, Stefan
AU  - Koračak, Ljiljana
AU  - Zlatović, Mario
AU  - Ilić-Tomić, Tatjana
AU  - Asakawa, Yoshinori
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor
PY  - 2020
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/3867
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3441
AB  - Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives
VL  - 142
SP  - 104520
DO  - 10.1016/j.fitote.2020.104520
ER  - 

@article{
author = "Novaković, Miroslav and Simić, Stefan and Koračak, Ljiljana and Zlatović, Mario and Ilić-Tomić, Tatjana and Asakawa, Yoshinori and Nikodinović-Runić, Jasmina and Opsenica, Igor",
year = "2020",
abstract = "Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives",
volume = "142",
pages = "104520",
doi = "10.1016/j.fitote.2020.104520"
}

Novaković, M., Simić, S., Koračak, L., Zlatović, M., Ilić-Tomić, T., Asakawa, Y., Nikodinović-Runić, J.,& Opsenica, I.. (2020). Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia
Elsevier., 142, 104520.
https://doi.org/10.1016/j.fitote.2020.104520

Novaković M, Simić S, Koračak L, Zlatović M, Ilić-Tomić T, Asakawa Y, Nikodinović-Runić J, Opsenica I. Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia. 2020;142:104520.
doi:10.1016/j.fitote.2020.104520 .

Novaković, Miroslav, Simić, Stefan, Koračak, Ljiljana, Zlatović, Mario, Ilić-Tomić, Tatjana, Asakawa, Yoshinori, Nikodinović-Runić, Jasmina, Opsenica, Igor, "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives" in Fitoterapia, 142 (2020):104520,
https://doi.org/10.1016/j.fitote.2020.104520 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Simić, Stefan
AU  - Koračak, Ljiljana
AU  - Zlatović, Mario
AU  - Ilić-Tomić, Tatjana
AU  - Asakawa, Yoshinori
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3449
AB  - Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives
VL  - 142
SP  - 104520
DO  - 10.1016/j.fitote.2020.104520
ER  - 

@article{
author = "Novaković, Miroslav and Simić, Stefan and Koračak, Ljiljana and Zlatović, Mario and Ilić-Tomić, Tatjana and Asakawa, Yoshinori and Nikodinović-Runić, Jasmina and Opsenica, Igor",
year = "2020",
abstract = "Chemical and biocatalytic synthesis of seven previously undescribed marchantin A ester derivatives has been presented. Chemical synthesis afforded three peresterified bisbibenzyl products (TE1-TE3), while enzymatic method, using lipase, produced regioselective monoester derivatives (ME1-ME4). The antiproliferative activities of all prepared derivatives of marchantin A were tested on MRC-5 healthy human lung fibroblast, A549 human lung cancer, and MDA-MB-231 human breast cancer cell lines. All tested esters were less cytotoxic in comparison to marchantin A, but they also exhibited lower cytotoxicity against healthy cells. Monoesters displayed higher cytotoxic activities than the corresponding peresterified products, presumably due to the presence of free catechol group. Monohexanoyl ester ME3 displayed the same IC50 like marchantin A against MDA-MB-231 cells, but the selectivity was higher. In this way, regioselective enzymatic monoesterification enhanced selectivity of marchantin A. ME3 was also the most active among all derivatives against lung cancer cells A549 with the slightly lower activity and selectivity in comparison to marchantin A.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives",
volume = "142",
pages = "104520",
doi = "10.1016/j.fitote.2020.104520"
}

Novaković, M., Simić, S., Koračak, L., Zlatović, M., Ilić-Tomić, T., Asakawa, Y., Nikodinović-Runić, J.,& Opsenica, I.. (2020). Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia
Elsevier., 142, 104520.
https://doi.org/10.1016/j.fitote.2020.104520

Novaković M, Simić S, Koračak L, Zlatović M, Ilić-Tomić T, Asakawa Y, Nikodinović-Runić J, Opsenica I. Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives. in Fitoterapia. 2020;142:104520.
doi:10.1016/j.fitote.2020.104520 .

Novaković, Miroslav, Simić, Stefan, Koračak, Ljiljana, Zlatović, Mario, Ilić-Tomić, Tatjana, Asakawa, Yoshinori, Nikodinović-Runić, Jasmina, Opsenica, Igor, "Chemo- and biocatalytic esterification of marchantin A and cytotoxic activity of ester derivatives" in Fitoterapia, 142 (2020):104520,
https://doi.org/10.1016/j.fitote.2020.104520 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Ilić-Tomić, Tatjana
AU  - Tešević, Vele
AU  - Simić, Katarina
AU  - Ivanović, Stefan
AU  - Simić, Stefan
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3639
AB  - The Trametes versicolor laccase catalyzed oxidation of chalcone butein afforded four dimers of aurone sulfuretin (i.e. two regioisomeric pairs of diasteromers, 1-4) as the major products. The formation of the dimers was explained by a two step process involving the initial cyclization of butein into aurone sulfuretin, followed by the combination of two molecules of sulfuretin. The coupling process occurred between the 2,10-double bond of one molecule of sulfuretin and the (3′,4′) catechol group of the other to yield a dimeric structure. This was confirmed by the experiment involving the laccase catalyzed oxidation of sulfuretin yielding the same dimeric bisaurones. Compounds 1, 3 and 4, were isolated using semipreparative HPLC and characterized by the detailed analysis of the NMR, MS, IR, and UV-vis data. The structure of compound 2, isolated as a mixture containing ca. 25% of compound 1, was proposed by the comparison of 1H NMR data to compound 1 and by using LC-ESIMS analysis. The starting chalcone butein and the products of the biocatalytic transformation, aurone sulfuretin and sulfuretin dimers 1, 3 and 4, were evaluated for their cytotoxic and antioxidative properties in vitro using a healthy human fibroblast (MRC5) cell line. The biotransformation products showed lower cytotoxicity but higher antioxidative properties. The C. coggygria bark methanol extract rich in butein and sulfuretin was also biotransformed by laccase. The transformed extract exhibited significantly improved antioxidative activities.
PB  - Royal Society of Chemistry
T2  - New Journal of Chemistry
T1  - Bisaurones-enzymatic production and biological evaluation
VL  - 44
IS  - 23
SP  - 9647
EP  - 9655
DO  - 10.1039/d0nj00758g
ER  - 

@article{
author = "Novaković, Miroslav and Ilić-Tomić, Tatjana and Tešević, Vele and Simić, Katarina and Ivanović, Stefan and Simić, Stefan and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2020",
abstract = "The Trametes versicolor laccase catalyzed oxidation of chalcone butein afforded four dimers of aurone sulfuretin (i.e. two regioisomeric pairs of diasteromers, 1-4) as the major products. The formation of the dimers was explained by a two step process involving the initial cyclization of butein into aurone sulfuretin, followed by the combination of two molecules of sulfuretin. The coupling process occurred between the 2,10-double bond of one molecule of sulfuretin and the (3′,4′) catechol group of the other to yield a dimeric structure. This was confirmed by the experiment involving the laccase catalyzed oxidation of sulfuretin yielding the same dimeric bisaurones. Compounds 1, 3 and 4, were isolated using semipreparative HPLC and characterized by the detailed analysis of the NMR, MS, IR, and UV-vis data. The structure of compound 2, isolated as a mixture containing ca. 25% of compound 1, was proposed by the comparison of 1H NMR data to compound 1 and by using LC-ESIMS analysis. The starting chalcone butein and the products of the biocatalytic transformation, aurone sulfuretin and sulfuretin dimers 1, 3 and 4, were evaluated for their cytotoxic and antioxidative properties in vitro using a healthy human fibroblast (MRC5) cell line. The biotransformation products showed lower cytotoxicity but higher antioxidative properties. The C. coggygria bark methanol extract rich in butein and sulfuretin was also biotransformed by laccase. The transformed extract exhibited significantly improved antioxidative activities.",
publisher = "Royal Society of Chemistry",
journal = "New Journal of Chemistry",
title = "Bisaurones-enzymatic production and biological evaluation",
volume = "44",
number = "23",
pages = "9647-9655",
doi = "10.1039/d0nj00758g"
}

Novaković, M., Ilić-Tomić, T., Tešević, V., Simić, K., Ivanović, S., Simić, S., Opsenica, I.,& Nikodinović-Runić, J.. (2020). Bisaurones-enzymatic production and biological evaluation. in New Journal of Chemistry
Royal Society of Chemistry., 44(23), 9647-9655.
https://doi.org/10.1039/d0nj00758g

Novaković M, Ilić-Tomić T, Tešević V, Simić K, Ivanović S, Simić S, Opsenica I, Nikodinović-Runić J. Bisaurones-enzymatic production and biological evaluation. in New Journal of Chemistry. 2020;44(23):9647-9655.
doi:10.1039/d0nj00758g .

Novaković, Miroslav, Ilić-Tomić, Tatjana, Tešević, Vele, Simić, Katarina, Ivanović, Stefan, Simić, Stefan, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Bisaurones-enzymatic production and biological evaluation" in New Journal of Chemistry, 44, no. 23 (2020):9647-9655,
https://doi.org/10.1039/d0nj00758g . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Ilić-Tomić, Tatjana
AU  - Tešević, Vele
AU  - Simić, Katarina
AU  - Ivanović, Stefan
AU  - Simić, Stefan
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3717
AB  - The Trametes versicolor laccase catalyzed oxidation of chalcone butein afforded four dimers of aurone sulfuretin (i.e. two regioisomeric pairs of diasteromers, 1-4) as the major products. The formation of the dimers was explained by a two step process involving the initial cyclization of butein into aurone sulfuretin, followed by the combination of two molecules of sulfuretin. The coupling process occurred between the 2,10-double bond of one molecule of sulfuretin and the (3′,4′) catechol group of the other to yield a dimeric structure. This was confirmed by the experiment involving the laccase catalyzed oxidation of sulfuretin yielding the same dimeric bisaurones. Compounds 1, 3 and 4, were isolated using semipreparative HPLC and characterized by the detailed analysis of the NMR, MS, IR, and UV-vis data. The structure of compound 2, isolated as a mixture containing ca. 25% of compound 1, was proposed by the comparison of 1H NMR data to compound 1 and by using LC-ESIMS analysis. The starting chalcone butein and the products of the biocatalytic transformation, aurone sulfuretin and sulfuretin dimers 1, 3 and 4, were evaluated for their cytotoxic and antioxidative properties in vitro using a healthy human fibroblast (MRC5) cell line. The biotransformation products showed lower cytotoxicity but higher antioxidative properties. The C. coggygria bark methanol extract rich in butein and sulfuretin was also biotransformed by laccase. The transformed extract exhibited significantly improved antioxidative activities.
PB  - Royal Society of Chemistry
T2  - New Journal of Chemistry
T1  - Bisaurones-enzymatic production and biological evaluation
VL  - 44
IS  - 23
SP  - 9647
EP  - 9655
DO  - 10.1039/d0nj00758g
ER  - 

@article{
author = "Novaković, Miroslav and Ilić-Tomić, Tatjana and Tešević, Vele and Simić, Katarina and Ivanović, Stefan and Simić, Stefan and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2020",
abstract = "The Trametes versicolor laccase catalyzed oxidation of chalcone butein afforded four dimers of aurone sulfuretin (i.e. two regioisomeric pairs of diasteromers, 1-4) as the major products. The formation of the dimers was explained by a two step process involving the initial cyclization of butein into aurone sulfuretin, followed by the combination of two molecules of sulfuretin. The coupling process occurred between the 2,10-double bond of one molecule of sulfuretin and the (3′,4′) catechol group of the other to yield a dimeric structure. This was confirmed by the experiment involving the laccase catalyzed oxidation of sulfuretin yielding the same dimeric bisaurones. Compounds 1, 3 and 4, were isolated using semipreparative HPLC and characterized by the detailed analysis of the NMR, MS, IR, and UV-vis data. The structure of compound 2, isolated as a mixture containing ca. 25% of compound 1, was proposed by the comparison of 1H NMR data to compound 1 and by using LC-ESIMS analysis. The starting chalcone butein and the products of the biocatalytic transformation, aurone sulfuretin and sulfuretin dimers 1, 3 and 4, were evaluated for their cytotoxic and antioxidative properties in vitro using a healthy human fibroblast (MRC5) cell line. The biotransformation products showed lower cytotoxicity but higher antioxidative properties. The C. coggygria bark methanol extract rich in butein and sulfuretin was also biotransformed by laccase. The transformed extract exhibited significantly improved antioxidative activities.",
publisher = "Royal Society of Chemistry",
journal = "New Journal of Chemistry",
title = "Bisaurones-enzymatic production and biological evaluation",
volume = "44",
number = "23",
pages = "9647-9655",
doi = "10.1039/d0nj00758g"
}

Novaković, M., Ilić-Tomić, T., Tešević, V., Simić, K., Ivanović, S., Simić, S., Opsenica, I.,& Nikodinović-Runić, J.. (2020). Bisaurones-enzymatic production and biological evaluation. in New Journal of Chemistry
Royal Society of Chemistry., 44(23), 9647-9655.
https://doi.org/10.1039/d0nj00758g

Novaković M, Ilić-Tomić T, Tešević V, Simić K, Ivanović S, Simić S, Opsenica I, Nikodinović-Runić J. Bisaurones-enzymatic production and biological evaluation. in New Journal of Chemistry. 2020;44(23):9647-9655.
doi:10.1039/d0nj00758g .

Novaković, Miroslav, Ilić-Tomić, Tatjana, Tešević, Vele, Simić, Katarina, Ivanović, Stefan, Simić, Stefan, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Bisaurones-enzymatic production and biological evaluation" in New Journal of Chemistry, 44, no. 23 (2020):9647-9655,
https://doi.org/10.1039/d0nj00758g . .

TY  - CONF
AU  - Simić, Stefan
AU  - Božić, Nataša
AU  - Đokić, Lidija
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor
PY  - 2019
UR  - https://www.shd.org.rs/index.php/abstracts-56
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3302
AB  - Laccases are a versatile class of enzymes with applications ranging from waste valorization to organic synthesis. We have tested whole-cell systems containing bacterial laccase as catalysts in the oxidation of 1,4-dihydropyridines. E. coli was used as the expression host for the cotA gene from Bacillus licheniformis, and the resulting whole-cell catalyst facilitated the oxidation of 1,4-dihydropyridines. It was found that multicopper oxidase CueO from the E. coli expression host also possesses catalytic activity in the oxidation of 1,4-dihydropyridines. The whole-cell biocatalyst expressing Bacillus licheniformis laccase was subsequently immobilized on bacterial nanocellulose and utilized in the same transformation, retaining 37 % of its original activity after three consecutive catalytic runs. This is the first report of a whole-cell catalytic system containing recombinant laccase for the oxidation of 1,4-dihydropyridines.
AB  - Lakaze predstavljalju raznoliku klasu enzima koja nalazi primenu od valorizacije otpada do organske sinteze. U ovom istraživanju ispitivane su cele ćelije koje sadrže bakterijsku lakazu kao katalizator u oksidaciji 1,4-dihidropiridina. Ekspresija cotA gena iz Bacillus licheniformis je izvršena u ćelijama E. coli i za nastali biokatalizator je ustanovljeno da ubrzava oksidaciju 1,4-dihidropiridina. Pored toga, ustanovljeno je da „multicopper“ oksidaza CueO iz E. coli takođe poseduje aktivnost prema oksidaciji 1,4-dihidropiridina. Ekspresioni sistem koji sadrži lakazu iz bakterije Bacillus licheniformis zatim je imobilizovan na bakterijskoj nanocelulozi i upotrebljen je kao katalizator u istoj transformaciji. Takav katalizator je bilo moguće ponovo upotrebiti tri puta, nakon čega je njegova aktivnost iznosila 37 % od početne. Navedeno istraživanje predstavlja prvu primenu celih ćelija sa rekombinantnom lakazom u oksidaciji 1,4-dihidropiridina.
PB  - Serbian Chemical Society, Belgrade / Srpsko hemijsko društvo, Beograd
C3  - 56th Meeting of the Serbian chemical Society - Book of Abstracts / 56. Savetovanje Srpskog hemijskog društva - Kratki izvodi radova, Niš 7-8.9. 2019.
T1  - Oxidation of 1,4-dihydropyridines catalyzed by recombinant bacterial laccase expressed in E. coli
T1  - Oksidacija 1,4-dihidropiridina katalizovana rekombinantnom bakterijskom lakazom eksprimiranom u E. coli
SP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_cer_3302
ER  - 

@conference{
author = "Simić, Stefan and Božić, Nataša and Đokić, Lidija and Nikodinović-Runić, Jasmina and Opsenica, Igor",
year = "2019",
abstract = "Laccases are a versatile class of enzymes with applications ranging from waste valorization to organic synthesis. We have tested whole-cell systems containing bacterial laccase as catalysts in the oxidation of 1,4-dihydropyridines. E. coli was used as the expression host for the cotA gene from Bacillus licheniformis, and the resulting whole-cell catalyst facilitated the oxidation of 1,4-dihydropyridines. It was found that multicopper oxidase CueO from the E. coli expression host also possesses catalytic activity in the oxidation of 1,4-dihydropyridines. The whole-cell biocatalyst expressing Bacillus licheniformis laccase was subsequently immobilized on bacterial nanocellulose and utilized in the same transformation, retaining 37 % of its original activity after three consecutive catalytic runs. This is the first report of a whole-cell catalytic system containing recombinant laccase for the oxidation of 1,4-dihydropyridines., Lakaze predstavljalju raznoliku klasu enzima koja nalazi primenu od valorizacije otpada do organske sinteze. U ovom istraživanju ispitivane su cele ćelije koje sadrže bakterijsku lakazu kao katalizator u oksidaciji 1,4-dihidropiridina. Ekspresija cotA gena iz Bacillus licheniformis je izvršena u ćelijama E. coli i za nastali biokatalizator je ustanovljeno da ubrzava oksidaciju 1,4-dihidropiridina. Pored toga, ustanovljeno je da „multicopper“ oksidaza CueO iz E. coli takođe poseduje aktivnost prema oksidaciji 1,4-dihidropiridina. Ekspresioni sistem koji sadrži lakazu iz bakterije Bacillus licheniformis zatim je imobilizovan na bakterijskoj nanocelulozi i upotrebljen je kao katalizator u istoj transformaciji. Takav katalizator je bilo moguće ponovo upotrebiti tri puta, nakon čega je njegova aktivnost iznosila 37 % od početne. Navedeno istraživanje predstavlja prvu primenu celih ćelija sa rekombinantnom lakazom u oksidaciji 1,4-dihidropiridina.",
publisher = "Serbian Chemical Society, Belgrade / Srpsko hemijsko društvo, Beograd",
journal = "56th Meeting of the Serbian chemical Society - Book of Abstracts / 56. Savetovanje Srpskog hemijskog društva - Kratki izvodi radova, Niš 7-8.9. 2019.",
title = "Oxidation of 1,4-dihydropyridines catalyzed by recombinant bacterial laccase expressed in E. coli, Oksidacija 1,4-dihidropiridina katalizovana rekombinantnom bakterijskom lakazom eksprimiranom u E. coli",
pages = "88",
url = "https://hdl.handle.net/21.15107/rcub_cer_3302"
}

Simić, S., Božić, N., Đokić, L., Nikodinović-Runić, J.,& Opsenica, I.. (2019). Oxidation of 1,4-dihydropyridines catalyzed by recombinant bacterial laccase expressed in E. coli. in 56th Meeting of the Serbian chemical Society - Book of Abstracts / 56. Savetovanje Srpskog hemijskog društva - Kratki izvodi radova, Niš 7-8.9. 2019.
Serbian Chemical Society, Belgrade / Srpsko hemijsko društvo, Beograd., 88.
https://hdl.handle.net/21.15107/rcub_cer_3302

Simić S, Božić N, Đokić L, Nikodinović-Runić J, Opsenica I. Oxidation of 1,4-dihydropyridines catalyzed by recombinant bacterial laccase expressed in E. coli. in 56th Meeting of the Serbian chemical Society - Book of Abstracts / 56. Savetovanje Srpskog hemijskog društva - Kratki izvodi radova, Niš 7-8.9. 2019.. 2019;:88.
https://hdl.handle.net/21.15107/rcub_cer_3302 .

Simić, Stefan, Božić, Nataša, Đokić, Lidija, Nikodinović-Runić, Jasmina, Opsenica, Igor, "Oxidation of 1,4-dihydropyridines catalyzed by recombinant bacterial laccase expressed in E. coli" in 56th Meeting of the Serbian chemical Society - Book of Abstracts / 56. Savetovanje Srpskog hemijskog društva - Kratki izvodi radova, Niš 7-8.9. 2019. (2019):88,
https://hdl.handle.net/21.15107/rcub_cer_3302 .

TY  - JOUR
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3211
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .

TY  - JOUR
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3342
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .

TY  - CONF
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3404
AB  - The aim of this study was to examine solubility-pH behavior of desipramine structural analogues:
imipramine and amitriptyline hydrochlorides. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult,
especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis
detection. Different techniques were used for solid phase characterization. Solid phase
characterization is particularly important in complicated systems like this.
PB  - International Association of Physical Chemists
C3  - 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
T1  - pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides
SP  - 51
EP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_cer_3404
ER  - 

@conference{
author = "Marković, Olivera and Pešić, Miloš P. and Avdeef, Alex and Verbić, Tatjana",
year = "2019",
abstract = "The aim of this study was to examine solubility-pH behavior of desipramine structural analogues:
imipramine and amitriptyline hydrochlorides. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult,
especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis
detection. Different techniques were used for solid phase characterization. Solid phase
characterization is particularly important in complicated systems like this.",
publisher = "International Association of Physical Chemists",
journal = "8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts",
title = "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides",
pages = "51-51",
url = "https://hdl.handle.net/21.15107/rcub_cer_3404"
}

Marković, O., Pešić, M. P., Avdeef, A.,& Verbić, T.. (2019). pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
International Association of Physical Chemists., 51-51.
https://hdl.handle.net/21.15107/rcub_cer_3404

Marković O, Pešić MP, Avdeef A, Verbić T. pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts. 2019;:51-51.
https://hdl.handle.net/21.15107/rcub_cer_3404 .

Marković, Olivera, Pešić, Miloš P., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides" in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts (2019):51-51,
https://hdl.handle.net/21.15107/rcub_cer_3404 .

TY  - CONF
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3405
AB  - The solution behavior of desipramine hydrochloride (DsHCl) in phosphate-buffered and unbuffered solutions is evidently complicated and only tentatively understood. The computer program pDISOL-X was used to design the structured pH-ramp shake flask experiments (pHRSF method), to process the data, and to refine the equilibrium constants.
PB  - International Association of Physical Chemists
C3  - 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
T1  - Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates
SP  - 17
EP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_cer_3405
ER  - 

@conference{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2019",
abstract = "The solution behavior of desipramine hydrochloride (DsHCl) in phosphate-buffered and unbuffered solutions is evidently complicated and only tentatively understood. The computer program pDISOL-X was used to design the structured pH-ramp shake flask experiments (pHRSF method), to process the data, and to refine the equilibrium constants.",
publisher = "International Association of Physical Chemists",
journal = "8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts",
title = "Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates",
pages = "17-17",
url = "https://hdl.handle.net/21.15107/rcub_cer_3405"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2019). Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
International Association of Physical Chemists., 17-17.
https://hdl.handle.net/21.15107/rcub_cer_3405

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Avdeef A, Verbić T. Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts. 2019;:17-17.
https://hdl.handle.net/21.15107/rcub_cer_3405 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates" in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts (2019):17-17,
https://hdl.handle.net/21.15107/rcub_cer_3405 .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3341
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Milojković-Opsenica, Dušanka
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2991
AB  - Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values
determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.
PB  - Elsevier
T2  - Journal of Chromatography B
T1  - Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands
VL  - 1124
SP  - 146
EP  - 153
DO  - 10.1016/j.jchromb.2019.06.006
ER  - 

@article{
author = "Šegan, Sandra and Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Milojković-Opsenica, Dušanka and Kostić Rajačić, Slađana",
year = "2019",
abstract = "Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values
determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.",
publisher = "Elsevier",
journal = "Journal of Chromatography B",
title = "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands",
volume = "1124",
pages = "146-153",
doi = "10.1016/j.jchromb.2019.06.006"
}

Šegan, S., Penjišević, J., Šukalović, V., Andrić, D., Milojković-Opsenica, D.,& Kostić Rajačić, S.. (2019). Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B
Elsevier., 1124, 146-153.
https://doi.org/10.1016/j.jchromb.2019.06.006

Šegan S, Penjišević J, Šukalović V, Andrić D, Milojković-Opsenica D, Kostić Rajačić S. Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B. 2019;1124:146-153.
doi:10.1016/j.jchromb.2019.06.006 .

Šegan, Sandra, Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Milojković-Opsenica, Dušanka, Kostić Rajačić, Slađana, "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands" in Journal of Chromatography B, 1124 (2019):146-153,
https://doi.org/10.1016/j.jchromb.2019.06.006 . .

TY  - JOUR
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2886
AB  - Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase
VL  - 308
SP  - 101
EP  - 109
DO  - 10.1016/j.cbi.2019.05.024
ER  - 

@article{
author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka",
year = "2019",
abstract = "Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase",
volume = "308",
pages = "101-109",
doi = "10.1016/j.cbi.2019.05.024"
}

Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 308, 101-109.
https://doi.org/10.1016/j.cbi.2019.05.024

Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions. 2019;308:101-109.
doi:10.1016/j.cbi.2019.05.024 .

Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase" in Chemico-Biological Interactions, 308 (2019):101-109,
https://doi.org/10.1016/j.cbi.2019.05.024 . .

TY  - JOUR
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2905
AB  - Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase
VL  - 308
SP  - 101
EP  - 109
DO  - 10.1016/j.cbi.2019.05.024
ER  - 

@article{
author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka",
year = "2019",
abstract = "Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase",
volume = "308",
pages = "101-109",
doi = "10.1016/j.cbi.2019.05.024"
}

Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 308, 101-109.
https://doi.org/10.1016/j.cbi.2019.05.024

Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions. 2019;308:101-109.
doi:10.1016/j.cbi.2019.05.024 .

Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase" in Chemico-Biological Interactions, 308 (2019):101-109,
https://doi.org/10.1016/j.cbi.2019.05.024 . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3205
AB  - Among widely used chromatographic methods modern thin-layer chromatography is not only the
simplest to perform but is also considered as respectable analytical method in various phases of
drug discovery and development processes such as monitoring of synthesis, identification of bioactive
substances from various natural sources and their isolation and purification, determination
of lipophilicity and other physico-chemical parameters, quantitative structure-activity relationship
studies, bioautography, as well as qualitative and quantitative analysis of drugs and their metabolites. An overview of recently published papers dealing with application of thin-layer chromatography in medicinal chemistry is presented.
PB  - Taylor & Francis Inc.
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Thin-layer chromatography in medicinal chemistry
VL  - 42
IS  - 9-10
SP  - 238
EP  - 248
DO  - 10.1080/10826076.2019.1585615
ER  - 

@article{
author = "Šegan, Sandra and Opsenica, Dejan and Milojković-Opsenica, Dušanka",
year = "2019",
abstract = "Among widely used chromatographic methods modern thin-layer chromatography is not only the
simplest to perform but is also considered as respectable analytical method in various phases of
drug discovery and development processes such as monitoring of synthesis, identification of bioactive
substances from various natural sources and their isolation and purification, determination
of lipophilicity and other physico-chemical parameters, quantitative structure-activity relationship
studies, bioautography, as well as qualitative and quantitative analysis of drugs and their metabolites. An overview of recently published papers dealing with application of thin-layer chromatography in medicinal chemistry is presented.",
publisher = "Taylor & Francis Inc.",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Thin-layer chromatography in medicinal chemistry",
volume = "42",
number = "9-10",
pages = "238-248",
doi = "10.1080/10826076.2019.1585615"
}

Šegan, S., Opsenica, D.,& Milojković-Opsenica, D.. (2019). Thin-layer chromatography in medicinal chemistry. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc.., 42(9-10), 238-248.
https://doi.org/10.1080/10826076.2019.1585615

Šegan S, Opsenica D, Milojković-Opsenica D. Thin-layer chromatography in medicinal chemistry. in Journal of Liquid Chromatography & Related Technologies. 2019;42(9-10):238-248.
doi:10.1080/10826076.2019.1585615 .

Šegan, Sandra, Opsenica, Dejan, Milojković-Opsenica, Dušanka, "Thin-layer chromatography in medicinal chemistry" in Journal of Liquid Chromatography & Related Technologies, 42, no. 9-10 (2019):238-248,
https://doi.org/10.1080/10826076.2019.1585615 . .

TY  - CHAP
AU  - Senerovic, Lidija
AU  - Opsenica, Dejan
AU  - Moric, Ivana
AU  - Aleksic, Ivana
AU  - Spasić, Marta
AU  - Vasiljevic, Branka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3094
AB  - Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.
PB  - Springer Nature
T2  - Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
T1  - Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents
DO  - 10.1007/5584_2019_428
ER  - 

@inbook{
author = "Senerovic, Lidija and Opsenica, Dejan and Moric, Ivana and Aleksic, Ivana and Spasić, Marta and Vasiljevic, Branka",
year = "2019",
abstract = "Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.",
publisher = "Springer Nature",
journal = "Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health",
booktitle = "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents",
doi = "10.1007/5584_2019_428"
}

Senerovic, L., Opsenica, D., Moric, I., Aleksic, I., Spasić, M.,& Vasiljevic, B.. (2019). Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
Springer Nature..
https://doi.org/10.1007/5584_2019_428

Senerovic L, Opsenica D, Moric I, Aleksic I, Spasić M, Vasiljevic B. Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health. 2019;.
doi:10.1007/5584_2019_428 .

Senerovic, Lidija, Opsenica, Dejan, Moric, Ivana, Aleksic, Ivana, Spasić, Marta, Vasiljevic, Branka, "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents" in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health (2019),
https://doi.org/10.1007/5584_2019_428 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Ristivojević, Petar
AU  - Pavić, Aleksandar
AU  - Radojević, Ivana
AU  - Čomić, Ljiljana R.
AU  - Vasiljević, Branka
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
AU  - Šenerović, Lidija
PY  - 2018
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/2932
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3139
AB  - Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts
VL  - 222
SP  - 148
EP  - 158
DO  - 10.1016/j.jep.2018.05.005
ER  - 

@article{
author = "Aleksić, Ivana and Ristivojević, Petar and Pavić, Aleksandar and Radojević, Ivana and Čomić, Ljiljana R. and Vasiljević, Branka and Opsenica, Dejan and Milojković-Opsenica, Dušanka and Šenerović, Lidija",
year = "2018",
abstract = "Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts",
volume = "222",
pages = "148-158",
doi = "10.1016/j.jep.2018.05.005"
}

Aleksić, I., Ristivojević, P., Pavić, A., Radojević, I., Čomić, L. R., Vasiljević, B., Opsenica, D., Milojković-Opsenica, D.,& Šenerović, L.. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 222, 148-158.
https://doi.org/10.1016/j.jep.2018.05.005

Aleksić I, Ristivojević P, Pavić A, Radojević I, Čomić LR, Vasiljević B, Opsenica D, Milojković-Opsenica D, Šenerović L. Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology. 2018;222:148-158.
doi:10.1016/j.jep.2018.05.005 .

Aleksić, Ivana, Ristivojević, Petar, Pavić, Aleksandar, Radojević, Ivana, Čomić, Ljiljana R., Vasiljević, Branka, Opsenica, Dejan, Milojković-Opsenica, Dušanka, Šenerović, Lidija, "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts" in Journal of Ethnopharmacology, 222 (2018):148-158,
https://doi.org/10.1016/j.jep.2018.05.005 . .

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Kiris, Erkan
AU  - Kota, Krishna P.
AU  - Kugelman-Tonos, Johanny
AU  - Videnović, Milica
AU  - Cazares, Lisa H.
AU  - Terzić-Jovanović, Nataša
AU  - Verbić, Tatjana
AU  - Anđelković, Boban D.
AU  - Duplantier, Allen J.
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2325
AB  - The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model
VL  - 61
IS  - 4
SP  - 1595
EP  - 1608
DO  - 10.1021/acs.jmedchem.7b01710
ER  - 

@article{
author = "Konstantinović, Jelena M. and Kiris, Erkan and Kota, Krishna P. and Kugelman-Tonos, Johanny and Videnović, Milica and Cazares, Lisa H. and Terzić-Jovanović, Nataša and Verbić, Tatjana and Anđelković, Boban D. and Duplantier, Allen J. and Bavari, Sina and Šolaja, Bogdan",
year = "2018",
abstract = "The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model",
volume = "61",
number = "4",
pages = "1595-1608",
doi = "10.1021/acs.jmedchem.7b01710"
}

Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B.. (2018). New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 61(4), 1595-1608.
https://doi.org/10.1021/acs.jmedchem.7b01710

Konstantinović JM, Kiris E, Kota KP, Kugelman-Tonos J, Videnović M, Cazares LH, Terzić-Jovanović N, Verbić T, Anđelković BD, Duplantier AJ, Bavari S, Šolaja B. New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry. 2018;61(4):1595-1608.
doi:10.1021/acs.jmedchem.7b01710 .

Konstantinović, Jelena M., Kiris, Erkan, Kota, Krishna P., Kugelman-Tonos, Johanny, Videnović, Milica, Cazares, Lisa H., Terzić-Jovanović, Nataša, Verbić, Tatjana, Anđelković, Boban D., Duplantier, Allen J., Bavari, Sina, Šolaja, Bogdan, "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model" in Journal of Medicinal Chemistry, 61, no. 4 (2018):1595-1608,
https://doi.org/10.1021/acs.jmedchem.7b01710 . .

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Videnović, Milica
AU  - Orsini, Stefania
AU  - Bogojević, Katarina
AU  - D'Alessandro, Sarah
AU  - Scaccabarozzi, Diletta
AU  - Terzić-Jovanović, Nataša
AU  - Gradoni, Luigi
AU  - Basilico, Nicoletta
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2428
AB  - In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.
PB  - American Chemical Society (ACS)
T2  - Acs Medicinal Chemistry Letters
T1  - Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice
VL  - 9
IS  - 7
SP  - 629
EP  - 634
DO  - 10.1021/acsmedchemlett.8b00053
ER  - 

@article{
author = "Konstantinović, Jelena M. and Videnović, Milica and Orsini, Stefania and Bogojević, Katarina and D'Alessandro, Sarah and Scaccabarozzi, Diletta and Terzić-Jovanović, Nataša and Gradoni, Luigi and Basilico, Nicoletta and Šolaja, Bogdan",
year = "2018",
abstract = "In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Medicinal Chemistry Letters",
title = "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice",
volume = "9",
number = "7",
pages = "629-634",
doi = "10.1021/acsmedchemlett.8b00053"
}

Konstantinović, J. M., Videnović, M., Orsini, S., Bogojević, K., D'Alessandro, S., Scaccabarozzi, D., Terzić-Jovanović, N., Gradoni, L., Basilico, N.,& Šolaja, B.. (2018). Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters
American Chemical Society (ACS)., 9(7), 629-634.
https://doi.org/10.1021/acsmedchemlett.8b00053

Konstantinović JM, Videnović M, Orsini S, Bogojević K, D'Alessandro S, Scaccabarozzi D, Terzić-Jovanović N, Gradoni L, Basilico N, Šolaja B. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters. 2018;9(7):629-634.
doi:10.1021/acsmedchemlett.8b00053 .

Konstantinović, Jelena M., Videnović, Milica, Orsini, Stefania, Bogojević, Katarina, D'Alessandro, Sarah, Scaccabarozzi, Diletta, Terzić-Jovanović, Nataša, Gradoni, Luigi, Basilico, Nicoletta, Šolaja, Bogdan, "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice" in Acs Medicinal Chemistry Letters, 9, no. 7 (2018):629-634,
https://doi.org/10.1021/acsmedchemlett.8b00053 . .

TY  - JOUR
AU  - Marković, Olivera
AU  - Cvijetić, Ilija
AU  - Zlatović, Mario
AU  - Opsenica, Igor
AU  - Konstantinović, Jelena M.
AU  - Terzić-Jovanović, Nataša
AU  - Šolaja, Bogdan
AU  - Verbić, Tatjana
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2472
AB  - Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy
T1  - Human serum albumin binding of certain antimalarials
VL  - 192
SP  - 128
EP  - 139
DO  - 10.1016/j.saa.2017.10.061
ER  - 

@article{
author = "Marković, Olivera and Cvijetić, Ilija and Zlatović, Mario and Opsenica, Igor and Konstantinović, Jelena M. and Terzić-Jovanović, Nataša and Šolaja, Bogdan and Verbić, Tatjana",
year = "2018",
abstract = "Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy",
title = "Human serum albumin binding of certain antimalarials",
volume = "192",
pages = "128-139",
doi = "10.1016/j.saa.2017.10.061"
}

Marković, O., Cvijetić, I., Zlatović, M., Opsenica, I., Konstantinović, J. M., Terzić-Jovanović, N., Šolaja, B.,& Verbić, T.. (2018). Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy
Oxford : Pergamon-Elsevier Science Ltd., 192, 128-139.
https://doi.org/10.1016/j.saa.2017.10.061

Marković O, Cvijetić I, Zlatović M, Opsenica I, Konstantinović JM, Terzić-Jovanović N, Šolaja B, Verbić T. Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy. 2018;192:128-139.
doi:10.1016/j.saa.2017.10.061 .

Marković, Olivera, Cvijetić, Ilija, Zlatović, Mario, Opsenica, Igor, Konstantinović, Jelena M., Terzić-Jovanović, Nataša, Šolaja, Bogdan, Verbić, Tatjana, "Human serum albumin binding of certain antimalarials" in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy, 192 (2018):128-139,
https://doi.org/10.1016/j.saa.2017.10.061 . .

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Kiris, Erkan
AU  - Kota, Krishna P.
AU  - Kugelman-Tonos, Johanny
AU  - Videnović, Milica
AU  - Cazares, Lisa H.
AU  - Terzić-Jovanović, Nataša
AU  - Verbić, Tatjana
AU  - Anđelković, Boban D.
AU  - Duplantier, Allen J.
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2935
AB  - The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model
VL  - 61
IS  - 4
SP  - 1595
EP  - 1608
DO  - 10.1021/acs.jmedchem.7b01710
ER  - 

@article{
author = "Konstantinović, Jelena M. and Kiris, Erkan and Kota, Krishna P. and Kugelman-Tonos, Johanny and Videnović, Milica and Cazares, Lisa H. and Terzić-Jovanović, Nataša and Verbić, Tatjana and Anđelković, Boban D. and Duplantier, Allen J. and Bavari, Sina and Šolaja, Bogdan",
year = "2018",
abstract = "The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model",
volume = "61",
number = "4",
pages = "1595-1608",
doi = "10.1021/acs.jmedchem.7b01710"
}

Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B.. (2018). New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 61(4), 1595-1608.
https://doi.org/10.1021/acs.jmedchem.7b01710

Konstantinović JM, Kiris E, Kota KP, Kugelman-Tonos J, Videnović M, Cazares LH, Terzić-Jovanović N, Verbić T, Anđelković BD, Duplantier AJ, Bavari S, Šolaja B. New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry. 2018;61(4):1595-1608.
doi:10.1021/acs.jmedchem.7b01710 .

Konstantinović, Jelena M., Kiris, Erkan, Kota, Krishna P., Kugelman-Tonos, Johanny, Videnović, Milica, Cazares, Lisa H., Terzić-Jovanović, Nataša, Verbić, Tatjana, Anđelković, Boban D., Duplantier, Allen J., Bavari, Sina, Šolaja, Bogdan, "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model" in Journal of Medicinal Chemistry, 61, no. 4 (2018):1595-1608,
https://doi.org/10.1021/acs.jmedchem.7b01710 . .

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Videnović, Milica
AU  - Orsini, Stefania
AU  - Bogojević, Katarina
AU  - D'Alessandro, Sarah
AU  - Scaccabarozzi, Diletta
AU  - Terzić-Jovanović, Nataša
AU  - Gradoni, Luigi
AU  - Basilico, Nicoletta
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3626
AB  - In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.
PB  - American Chemical Society (ACS)
T2  - Acs Medicinal Chemistry Letters
T1  - Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice
VL  - 9
IS  - 7
SP  - 629
EP  - 634
DO  - 10.1021/acsmedchemlett.8b00053
ER  - 

@article{
author = "Konstantinović, Jelena M. and Videnović, Milica and Orsini, Stefania and Bogojević, Katarina and D'Alessandro, Sarah and Scaccabarozzi, Diletta and Terzić-Jovanović, Nataša and Gradoni, Luigi and Basilico, Nicoletta and Šolaja, Bogdan",
year = "2018",
abstract = "In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Medicinal Chemistry Letters",
title = "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice",
volume = "9",
number = "7",
pages = "629-634",
doi = "10.1021/acsmedchemlett.8b00053"
}

Konstantinović, J. M., Videnović, M., Orsini, S., Bogojević, K., D'Alessandro, S., Scaccabarozzi, D., Terzić-Jovanović, N., Gradoni, L., Basilico, N.,& Šolaja, B.. (2018). Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters
American Chemical Society (ACS)., 9(7), 629-634.
https://doi.org/10.1021/acsmedchemlett.8b00053

Konstantinović JM, Videnović M, Orsini S, Bogojević K, D'Alessandro S, Scaccabarozzi D, Terzić-Jovanović N, Gradoni L, Basilico N, Šolaja B. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters. 2018;9(7):629-634.
doi:10.1021/acsmedchemlett.8b00053 .

Konstantinović, Jelena M., Videnović, Milica, Orsini, Stefania, Bogojević, Katarina, D'Alessandro, Sarah, Scaccabarozzi, Diletta, Terzić-Jovanović, Nataša, Gradoni, Luigi, Basilico, Nicoletta, Šolaja, Bogdan, "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice" in Acs Medicinal Chemistry Letters, 9, no. 7 (2018):629-634,
https://doi.org/10.1021/acsmedchemlett.8b00053 . .

TY  - DATA
AU  - Konstantinović, Jelena M.
AU  - Kiris, Erkan
AU  - Kota, Krishna P.
AU  - Kugelman-Tonos, Johanny
AU  - Videnović, Milica
AU  - Cazares, Lisa H.
AU  - Terzić-Jovanović, Nataša
AU  - Verbić, Tatjana
AU  - Anđelković, Boban D.
AU  - Duplantier, Allen J.
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4515
AB  - Inhibitory activities against BoNT/A LC and holotoxin in proteolytic and cell-based assay for all tested compounds; fluorescence and UV–vis spectra for determination of 16 binding to HSA and AGP; ligand interaction diagrams, docking scores, and docking–in vitro inhibitory activity correlations; spectral and analytical data for all synthesized compounds; detailed procedures for the determination of the HPLC purity.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - Supporting Information I for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model"
DO  - 10.1021/acs.jmedchem.7b01710.s001
ER  - 

@misc{
author = "Konstantinović, Jelena M. and Kiris, Erkan and Kota, Krishna P. and Kugelman-Tonos, Johanny and Videnović, Milica and Cazares, Lisa H. and Terzić-Jovanović, Nataša and Verbić, Tatjana and Anđelković, Boban D. and Duplantier, Allen J. and Bavari, Sina and Šolaja, Bogdan",
year = "2018",
abstract = "Inhibitory activities against BoNT/A LC and holotoxin in proteolytic and cell-based assay for all tested compounds; fluorescence and UV–vis spectra for determination of 16 binding to HSA and AGP; ligand interaction diagrams, docking scores, and docking–in vitro inhibitory activity correlations; spectral and analytical data for all synthesized compounds; detailed procedures for the determination of the HPLC purity.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "Supporting Information I for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model"",
doi = "10.1021/acs.jmedchem.7b01710.s001"
}

Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B.. (2018). Supporting Information I for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model". in Journal of Medicinal Chemistry
American Chemical Society (ACS)..
https://doi.org/10.1021/acs.jmedchem.7b01710.s001

Konstantinović JM, Kiris E, Kota KP, Kugelman-Tonos J, Videnović M, Cazares LH, Terzić-Jovanović N, Verbić T, Anđelković BD, Duplantier AJ, Bavari S, Šolaja B. Supporting Information I for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model". in Journal of Medicinal Chemistry. 2018;.
doi:10.1021/acs.jmedchem.7b01710.s001 .

Konstantinović, Jelena M., Kiris, Erkan, Kota, Krishna P., Kugelman-Tonos, Johanny, Videnović, Milica, Cazares, Lisa H., Terzić-Jovanović, Nataša, Verbić, Tatjana, Anđelković, Boban D., Duplantier, Allen J., Bavari, Sina, Šolaja, Bogdan, "Supporting Information I for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model"" in Journal of Medicinal Chemistry (2018),
https://doi.org/10.1021/acs.jmedchem.7b01710.s001 . .