TY  - JOUR
AU  - Platanić Arizanović, Lena
AU  - Gligorijević, Nikola
AU  - Cvijetić, Ilija
AU  - Mijatović, Aleksandar
AU  - Krstić Ristivojević, Maja
AU  - Minić, Simeon
AU  - Nikolić Kokić, Aleksandra
AU  - Miljević, Čedo
AU  - Nikolić, Milan
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6482
AB  - Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van’t Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ  interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~10^4 M^-1), the highest observed for clozapine (2.2 x 10^4 M^-1 at 25 °C). The clozapine binding showed “friendly” effects: increased α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation. On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed.
PB  - Multidisciplinary Digital Publishing Institute (MDPI)
T2  - International Journal of Molecular Sciences
T1  - Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
VL  - 24
IS  - 10
SP  - 8921
DO  - 10.3390/ijms24108921
ER  - 

@article{
author = "Platanić Arizanović, Lena and Gligorijević, Nikola and Cvijetić, Ilija and Mijatović, Aleksandar and Krstić Ristivojević, Maja and Minić, Simeon and Nikolić Kokić, Aleksandra and Miljević, Čedo and Nikolić, Milan",
year = "2023",
abstract = "Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van’t Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ  interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~10^4 M^-1), the highest observed for clozapine (2.2 x 10^4 M^-1 at 25 °C). The clozapine binding showed “friendly” effects: increased α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation. On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed.",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "International Journal of Molecular Sciences",
title = "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?",
volume = "24",
number = "10",
pages = "8921",
doi = "10.3390/ijms24108921"
}

Platanić Arizanović, L., Gligorijević, N., Cvijetić, I., Mijatović, A., Krstić Ristivojević, M., Minić, S., Nikolić Kokić, A., Miljević, Č.,& Nikolić, M.. (2023). Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences
Multidisciplinary Digital Publishing Institute (MDPI)., 24(10), 8921.
https://doi.org/10.3390/ijms24108921

Platanić Arizanović L, Gligorijević N, Cvijetić I, Mijatović A, Krstić Ristivojević M, Minić S, Nikolić Kokić A, Miljević Č, Nikolić M. Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences. 2023;24(10):8921.
doi:10.3390/ijms24108921 .

Platanić Arizanović, Lena, Gligorijević, Nikola, Cvijetić, Ilija, Mijatović, Aleksandar, Krstić Ristivojević, Maja, Minić, Simeon, Nikolić Kokić, Aleksandra, Miljević, Čedo, Nikolić, Milan, "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?" in International Journal of Molecular Sciences, 24, no. 10 (2023):8921,
https://doi.org/10.3390/ijms24108921 . .

TY  - JOUR
AU  - Mijatović, Aleksandar
AU  - Gligorijević, Nevenka
AU  - Ćoćić, Dušan
AU  - Spasić, Snežana
AU  - Lolić, Aleksandar
AU  - Aranđelović, Sandra
AU  - Nikolić, Milan
AU  - Baošić, Rada
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6777
AB  - The biological activity of six structurally similar tetradentate Schiff base copper(II) complexes, namely [Cu(ethylenediamine-bis-acetylacetonate)] (CuAA) and five derivatives where two methyl groups are replaced by phenyl, (CuPP), CF3 (CuTT) or by mixed groups CH3/CF3 (CuAT), Ph/CF3 (CuPT), and Ph/CH3 (CuAP) has been investigated. The set of antioxidant assays was performed, and the results were expressed as IC50 and EC50 values. The series of complexes showed interesting bioactivity and were investigated for the determination of antioxidant, antifungal, antimicrobial, and cytotoxic activity. A significant antioxidant behavior was exhibited by complex CuAA, greater than Trolox in the Oxygen Radical Absorbance Capacity (ORAC) assay. Antibacterial assay over Gram-positive and Gram-negative pathogenic bacterial strains and some fungal pathogens were studied. Antiproliferative activity of complexes in two human tumor cell lines, breast adenocarcinoma MCF-7, colon adenocarcinoma LS-174, and normal fibroblast cells-MRC-5, examined the effect on cell cycle progression. The significant cytotoxic potential, comparable to cisplatin cytotoxicity, was determined in human breast cancer cell line-MCF-7 with IC50 values being 17.53–31.40 μM and human colon cancer cell line-LS-174 with IC50 values being 15.22–23.92 μM. All tested compounds showed nearly twice more selectivity toward cancer cell lines than normal cells. The interactions of complexes with human serum albumin (HSA), the most prominent protein in plasma, were investigated using spectroscopic fluorescence techniques. The complexes bind to human serum albumin at multiple sites (n = 0.2–1.9), displaying a moderate binding constant Ka = 4.1–12.4 × 104 M−1. The molecular docking experiment effectively showed complex binding to HSA and DNA molecular fragments.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge
VL  - 244
SP  - 112224
DO  - 10.1016/j.jinorgbio.2023.112224
ER  - 

@article{
author = "Mijatović, Aleksandar and Gligorijević, Nevenka and Ćoćić, Dušan and Spasić, Snežana and Lolić, Aleksandar and Aranđelović, Sandra and Nikolić, Milan and Baošić, Rada",
year = "2023",
abstract = "The biological activity of six structurally similar tetradentate Schiff base copper(II) complexes, namely [Cu(ethylenediamine-bis-acetylacetonate)] (CuAA) and five derivatives where two methyl groups are replaced by phenyl, (CuPP), CF3 (CuTT) or by mixed groups CH3/CF3 (CuAT), Ph/CF3 (CuPT), and Ph/CH3 (CuAP) has been investigated. The set of antioxidant assays was performed, and the results were expressed as IC50 and EC50 values. The series of complexes showed interesting bioactivity and were investigated for the determination of antioxidant, antifungal, antimicrobial, and cytotoxic activity. A significant antioxidant behavior was exhibited by complex CuAA, greater than Trolox in the Oxygen Radical Absorbance Capacity (ORAC) assay. Antibacterial assay over Gram-positive and Gram-negative pathogenic bacterial strains and some fungal pathogens were studied. Antiproliferative activity of complexes in two human tumor cell lines, breast adenocarcinoma MCF-7, colon adenocarcinoma LS-174, and normal fibroblast cells-MRC-5, examined the effect on cell cycle progression. The significant cytotoxic potential, comparable to cisplatin cytotoxicity, was determined in human breast cancer cell line-MCF-7 with IC50 values being 17.53–31.40 μM and human colon cancer cell line-LS-174 with IC50 values being 15.22–23.92 μM. All tested compounds showed nearly twice more selectivity toward cancer cell lines than normal cells. The interactions of complexes with human serum albumin (HSA), the most prominent protein in plasma, were investigated using spectroscopic fluorescence techniques. The complexes bind to human serum albumin at multiple sites (n = 0.2–1.9), displaying a moderate binding constant Ka = 4.1–12.4 × 104 M−1. The molecular docking experiment effectively showed complex binding to HSA and DNA molecular fragments.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge",
volume = "244",
pages = "112224",
doi = "10.1016/j.jinorgbio.2023.112224"
}

Mijatović, A., Gligorijević, N., Ćoćić, D., Spasić, S., Lolić, A., Aranđelović, S., Nikolić, M.,& Baošić, R.. (2023). In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge. in Journal of Inorganic Biochemistry
Elsevier., 244, 112224.
https://doi.org/10.1016/j.jinorgbio.2023.112224

Mijatović A, Gligorijević N, Ćoćić D, Spasić S, Lolić A, Aranđelović S, Nikolić M, Baošić R. In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge. in Journal of Inorganic Biochemistry. 2023;244:112224.
doi:10.1016/j.jinorgbio.2023.112224 .

Mijatović, Aleksandar, Gligorijević, Nevenka, Ćoćić, Dušan, Spasić, Snežana, Lolić, Aleksandar, Aranđelović, Sandra, Nikolić, Milan, Baošić, Rada, "In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge" in Journal of Inorganic Biochemistry, 244 (2023):112224,
https://doi.org/10.1016/j.jinorgbio.2023.112224 . .