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 . .