Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
Autori
Platanić Arizanović, LenaGligorijević, Nikola
Cvijetić, Ilija
Mijatović, Aleksandar
Krstić Ristivojević, Maja
Minić, Simeon
Nikolić Kokić, Aleksandra
Miljević, Čedo
Nikolić, Milan
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 ha...nd, 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.
Ključne reči:
antipsychotics / human hemoglobin / clozapine / ziprasidone / sertindole / binding / interactionsIzvor:
International Journal of Molecular Sciences, 2023, 24, 10, 8921-Izdavač:
- Multidisciplinary Digital Publishing Institute (MDPI)
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-MESTD-inst-2020-200168)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-MESTD-inst-2020-200026)
DOI: 10.3390/ijms24108921
ISSN: 1422-0067
PubMed: 37240267
Scopus: 2-s2.0-85160374364
Institucija/grupa
IHTMTY - 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 . .