TY  - JOUR
AU  - Ivković, Ivana
AU  - Bukvicki, Danka
AU  - Novaković, Miroslav
AU  - Majstorović, Ivana
AU  - Leskovac, Andreja
AU  - Petrović, Sandra
AU  - Veljić, Milan
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4894
AB  - Liverworts are characterized by a high content of bioactive compounds reported to show antimicrobial, anticancer, and antioxidant properties. In this study, the biological effects of the methanol extract of the liverwort Pellia endiviifolia and its constituents, bis-bibenzyls perrottetin E, 10′-hydroxyperrottetin E, and 10,10′-dihydroxyperrottetin E, were investigated using human peripheral blood cells as a model system. The assessment of the investigated compounds comprised testing their genotoxicity, apoptotic potential, and redox modulating activities. The genotoxicity testing indicated that medium (25 µM) and high concentrations (100 µM) of the investigated compounds displayed genotoxic and antiproliferative effects in human lymphocytes as revealed by significant, concentration-dependent enhancement of the micronuclei incidence and decrease in the cytokinesis-block proliferation index compared to the control (P <.001). Analysis of leukocyte apoptosis showed a substantial potential of all investigated compounds to induce apoptosis, which was not concentration-dependent. The P endiviifolia extract and perrottetin E demonstrated considerable pro-apoptotic potential, even at the lowest concentration (1 µM) applied. Evaluation of the redox modulating effects, which comprised measuring erythrocyte catalase activity and the lymphocyte malondialdehyde level, showed that the investigated compounds did not induce oxidative stress in human peripheral blood cells (P >.05). The observed genotoxic, antiproliferative, and proapoptotic effects of the investigated compounds make them suitable for further comprehensive studies related to their possible applications as anticancer agents.
PB  - SAGE Publications Inc.
T2  - Natural Product Communications
T1  - Assessment of the Biological Effects of Pellia endiviifolia and its Constituents in Vitro
VL  - 16
IS  - 11
SP  - 1
EP  - 9
DO  - 10.1177/1934578X211056422
ER  - 

@article{
author = "Ivković, Ivana and Bukvicki, Danka and Novaković, Miroslav and Majstorović, Ivana and Leskovac, Andreja and Petrović, Sandra and Veljić, Milan",
year = "2021",
abstract = "Liverworts are characterized by a high content of bioactive compounds reported to show antimicrobial, anticancer, and antioxidant properties. In this study, the biological effects of the methanol extract of the liverwort Pellia endiviifolia and its constituents, bis-bibenzyls perrottetin E, 10′-hydroxyperrottetin E, and 10,10′-dihydroxyperrottetin E, were investigated using human peripheral blood cells as a model system. The assessment of the investigated compounds comprised testing their genotoxicity, apoptotic potential, and redox modulating activities. The genotoxicity testing indicated that medium (25 µM) and high concentrations (100 µM) of the investigated compounds displayed genotoxic and antiproliferative effects in human lymphocytes as revealed by significant, concentration-dependent enhancement of the micronuclei incidence and decrease in the cytokinesis-block proliferation index compared to the control (P <.001). Analysis of leukocyte apoptosis showed a substantial potential of all investigated compounds to induce apoptosis, which was not concentration-dependent. The P endiviifolia extract and perrottetin E demonstrated considerable pro-apoptotic potential, even at the lowest concentration (1 µM) applied. Evaluation of the redox modulating effects, which comprised measuring erythrocyte catalase activity and the lymphocyte malondialdehyde level, showed that the investigated compounds did not induce oxidative stress in human peripheral blood cells (P >.05). The observed genotoxic, antiproliferative, and proapoptotic effects of the investigated compounds make them suitable for further comprehensive studies related to their possible applications as anticancer agents.",
publisher = "SAGE Publications Inc.",
journal = "Natural Product Communications",
title = "Assessment of the Biological Effects of Pellia endiviifolia and its Constituents in Vitro",
volume = "16",
number = "11",
pages = "1-9",
doi = "10.1177/1934578X211056422"
}

Ivković, I., Bukvicki, D., Novaković, M., Majstorović, I., Leskovac, A., Petrović, S.,& Veljić, M.. (2021). Assessment of the Biological Effects of Pellia endiviifolia and its Constituents in Vitro. in Natural Product Communications
SAGE Publications Inc.., 16(11), 1-9.
https://doi.org/10.1177/1934578X211056422

Ivković I, Bukvicki D, Novaković M, Majstorović I, Leskovac A, Petrović S, Veljić M. Assessment of the Biological Effects of Pellia endiviifolia and its Constituents in Vitro. in Natural Product Communications. 2021;16(11):1-9.
doi:10.1177/1934578X211056422 .

Ivković, Ivana, Bukvicki, Danka, Novaković, Miroslav, Majstorović, Ivana, Leskovac, Andreja, Petrović, Sandra, Veljić, Milan, "Assessment of the Biological Effects of Pellia endiviifolia and its Constituents in Vitro" in Natural Product Communications, 16, no. 11 (2021):1-9,
https://doi.org/10.1177/1934578X211056422 . .

TY  - JOUR
AU  - Bondžić, Aleksandra M.
AU  - Lazarević-Pašti, Tamara D.
AU  - Leskovac, Andreja R.
AU  - Petrović, Sandra
AU  - Čolović, Mirjana B.
AU  - Parac-Vogt Tatjana
AU  - Janjić, Goran
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3582
AB  - Acetylcholinesterase (AChE) inhibitors are important in the treatment of neurodegenerative diseases. Two inhibitors,
12-tungstosilicic acid (WSiA) and 12-tungstophosphoric acid (WPA), which have polyoxometalate
(POM) type structure, have been shown to inhibit AChE activity in nM concentration. Circular dichroism and
tryptophan fluorescence spectroscopy demonstrated that the AChE inhibition was not accompanied by significant
changes in the secondary structure of the enzyme. The molecular docking approach has revealed a new
allosteric binding site, termed β-allosteric site (β-AS), which is considered responsible for the inhibition of AChE
by POMs. To the best of our knowledge, this is the first study reporting a new allosteric site that is considered
responsible for AChE inhibition by voluminous and negatively charged molecules such as POMs. The selected
POMs were further subjected to genotoxicity testing using human peripheral blood cells as a model system. It
was shown that WSiA and WPA induced a mild cytostatic but not genotoxic effects in human lymphocytes, which
indicates their potential to be used as medicinal drugs. The identification of non-toxic compounds capable of
binding to an allosteric site that so far has not been considered responsible for enzyme inhibition could be
fundamental for the development of new drug design strategies and the discovery of more efficient AChE
modulators.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules – the role in the mechanism of AChE inhibition
VL  - 151
SP  - 105376
DO  - 10.1016/j.ejps.2020.105376
ER  - 

@article{
author = "Bondžić, Aleksandra M. and Lazarević-Pašti, Tamara D. and Leskovac, Andreja R. and Petrović, Sandra and Čolović, Mirjana B. and Parac-Vogt Tatjana and Janjić, Goran",
year = "2020",
abstract = "Acetylcholinesterase (AChE) inhibitors are important in the treatment of neurodegenerative diseases. Two inhibitors,
12-tungstosilicic acid (WSiA) and 12-tungstophosphoric acid (WPA), which have polyoxometalate
(POM) type structure, have been shown to inhibit AChE activity in nM concentration. Circular dichroism and
tryptophan fluorescence spectroscopy demonstrated that the AChE inhibition was not accompanied by significant
changes in the secondary structure of the enzyme. The molecular docking approach has revealed a new
allosteric binding site, termed β-allosteric site (β-AS), which is considered responsible for the inhibition of AChE
by POMs. To the best of our knowledge, this is the first study reporting a new allosteric site that is considered
responsible for AChE inhibition by voluminous and negatively charged molecules such as POMs. The selected
POMs were further subjected to genotoxicity testing using human peripheral blood cells as a model system. It
was shown that WSiA and WPA induced a mild cytostatic but not genotoxic effects in human lymphocytes, which
indicates their potential to be used as medicinal drugs. The identification of non-toxic compounds capable of
binding to an allosteric site that so far has not been considered responsible for enzyme inhibition could be
fundamental for the development of new drug design strategies and the discovery of more efficient AChE
modulators.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules – the role in the mechanism of AChE inhibition",
volume = "151",
pages = "105376",
doi = "10.1016/j.ejps.2020.105376"
}

Bondžić, A. M., Lazarević-Pašti, T. D., Leskovac, A. R., Petrović, S., Čolović, M. B., Parac-Vogt Tatjana,& Janjić, G.. (2020). A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules – the role in the mechanism of AChE inhibition. in European Journal of Pharmaceutical Sciences
Elsevier., 151, 105376.
https://doi.org/10.1016/j.ejps.2020.105376

Bondžić AM, Lazarević-Pašti TD, Leskovac AR, Petrović S, Čolović MB, Parac-Vogt Tatjana, Janjić G. A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules – the role in the mechanism of AChE inhibition. in European Journal of Pharmaceutical Sciences. 2020;151:105376.
doi:10.1016/j.ejps.2020.105376 .

Bondžić, Aleksandra M., Lazarević-Pašti, Tamara D., Leskovac, Andreja R., Petrović, Sandra, Čolović, Mirjana B., Parac-Vogt Tatjana, Janjić, Goran, "A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules – the role in the mechanism of AChE inhibition" in European Journal of Pharmaceutical Sciences, 151 (2020):105376,
https://doi.org/10.1016/j.ejps.2020.105376 . .

TY  - JOUR
AU  - Bondžić, Aleksandra M.
AU  - Čolović, Mirjana B.
AU  - Janjić, Goran
AU  - Zarić, Božidarka
AU  - Petrović, Sandra
AU  - Krstic, Danijela Z.
AU  - Marzo, Tiziano
AU  - Messori, Luigi
AU  - Vasić, Vesna M.
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2143
AB  - The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e., [(bipy2Me)(2)Au-2(mu-O)(2)][PF6](2) (Auoxo6), Au-2[(bipydmb-H)(2)(mu-O)][PF6] (Au(2)bipyC) and [Au-2(phen(2Me))(2)(mu-O)(2)](PF6)(2) (Au(2)phen) on Na/K-ATPase, purified from the porcine cerebral cortex, were investigated. All three studied gold complexes inhibited the enzyme activity in a concentration-dependent manner achieving IC50 values in the low micromolar range. Kinetic analysis suggested an uncompetitive mode of inhibition for Auoxo6 and Au(2)bipyC, and a mixed type one for Au(2)phen. Docking studies indicated that the inhibitory actions of all tested complexes are related to E2-P enzyme conformation binding to ion channel and intracellular part between N and P sub-domain. In addition, Au(2)phen was able to inhibit the enzyme by interacting with its extracellular part as well. Toxic effects of the gold(III) complexes were evaluated in vitro by following lactate dehydrogenase activity in rat brain synaptosomes and incidence of micronuclei and cytokinesis-block proliferation index in cultivated human lymphocytes. All investigated complexes turned out to induce cytogenetic damage consisting of a significant decrease in cell proliferation and an increase in micronuclei in a dose-dependent manner. On the other hand, lactate dehydrogenase activity, an indicator of membrane integrity/viability, was not affected by Auoxo6 and Au(2)bipyC, while Au(2)phen slightly modified its activity.
PB  - Springer, New York
T2  - Journal of Biological Inorganic Chemistry
T1  - The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach
VL  - 22
IS  - 6
SP  - 819
EP  - 832
DO  - 10.1007/s00775-017-1460-5
ER  - 

@article{
author = "Bondžić, Aleksandra M. and Čolović, Mirjana B. and Janjić, Goran and Zarić, Božidarka and Petrović, Sandra and Krstic, Danijela Z. and Marzo, Tiziano and Messori, Luigi and Vasić, Vesna M.",
year = "2017",
abstract = "The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e., [(bipy2Me)(2)Au-2(mu-O)(2)][PF6](2) (Auoxo6), Au-2[(bipydmb-H)(2)(mu-O)][PF6] (Au(2)bipyC) and [Au-2(phen(2Me))(2)(mu-O)(2)](PF6)(2) (Au(2)phen) on Na/K-ATPase, purified from the porcine cerebral cortex, were investigated. All three studied gold complexes inhibited the enzyme activity in a concentration-dependent manner achieving IC50 values in the low micromolar range. Kinetic analysis suggested an uncompetitive mode of inhibition for Auoxo6 and Au(2)bipyC, and a mixed type one for Au(2)phen. Docking studies indicated that the inhibitory actions of all tested complexes are related to E2-P enzyme conformation binding to ion channel and intracellular part between N and P sub-domain. In addition, Au(2)phen was able to inhibit the enzyme by interacting with its extracellular part as well. Toxic effects of the gold(III) complexes were evaluated in vitro by following lactate dehydrogenase activity in rat brain synaptosomes and incidence of micronuclei and cytokinesis-block proliferation index in cultivated human lymphocytes. All investigated complexes turned out to induce cytogenetic damage consisting of a significant decrease in cell proliferation and an increase in micronuclei in a dose-dependent manner. On the other hand, lactate dehydrogenase activity, an indicator of membrane integrity/viability, was not affected by Auoxo6 and Au(2)bipyC, while Au(2)phen slightly modified its activity.",
publisher = "Springer, New York",
journal = "Journal of Biological Inorganic Chemistry",
title = "The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach",
volume = "22",
number = "6",
pages = "819-832",
doi = "10.1007/s00775-017-1460-5"
}

Bondžić, A. M., Čolović, M. B., Janjić, G., Zarić, B., Petrović, S., Krstic, D. Z., Marzo, T., Messori, L.,& Vasić, V. M.. (2017). The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach. in Journal of Biological Inorganic Chemistry
Springer, New York., 22(6), 819-832.
https://doi.org/10.1007/s00775-017-1460-5

Bondžić AM, Čolović MB, Janjić G, Zarić B, Petrović S, Krstic DZ, Marzo T, Messori L, Vasić VM. The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach. in Journal of Biological Inorganic Chemistry. 2017;22(6):819-832.
doi:10.1007/s00775-017-1460-5 .

Bondžić, Aleksandra M., Čolović, Mirjana B., Janjić, Goran, Zarić, Božidarka, Petrović, Sandra, Krstic, Danijela Z., Marzo, Tiziano, Messori, Luigi, Vasić, Vesna M., "The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach" in Journal of Biological Inorganic Chemistry, 22, no. 6 (2017):819-832,
https://doi.org/10.1007/s00775-017-1460-5 . .