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  - http://radar.ibiss.bg.ac.rs/handle/123456789/6028
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 (~104 M−1
), the highest observed
for clozapine (2.2 × 104 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  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
IS  - 10
VL  - 24
DO  - 10.3390/ijms24108921
SP  - 8921
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 (~104 M−1
), the highest observed
for clozapine (2.2 × 104 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 = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?",
number = "10",
volume = "24",
doi = "10.3390/ijms24108921",
pages = "8921"
}

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
Basel: 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 . .