The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach
Само за регистроване кориснике
2017
Аутори
Bondžić, Aleksandra M.Čolović, Mirjana B.
Janjić, Goran
Zarić, Božidarka
Petrović, Sandra
Krstic, Danijela Z.
Marzo, Tiziano
Messori, Luigi
Vasić, Vesna M.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 synaptos...omes 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.
Кључне речи:
Binuclear gold(III) complexes / Na/K-ATPase / Inhibition / Docking studies / Cytotoxicity / GenotoxicityИзвор:
Journal of Biological Inorganic Chemistry, 2017, 22, 6, 819-832Издавач:
- Springer, New York
Финансирање / пројекти:
- Истраживања интеракција ензима са токсичним и фармаколошки активним молекулима (RS-172023)
- Beneficentia Stiftung (Vaduz)
- ITT (Istituto Toscano Tumori)
- Fondazione Cassa Risparmio Firenze (CRF)
- AIRC - IG-16049
- AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro) - 18044
DOI: 10.1007/s00775-017-1460-5
ISSN: 0949-8257
PubMed: 28432453
WoS: 000406036700003
Scopus: 2-s2.0-85018825607
Институција/група
IHTMTY - 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 . .