Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?

Објеката

Тип
Рад у часопису
Верзија рада
објављена верзија
Језик
енглески
Креатор
Lena Platanić Arizanović, Nikola Gligorijević, Ilija Cvijetić, Aleksandar Mijatović, Maja Krstić Ristivojević, Simeon Minić, Aleksandra Nikolić Kokić, Čedo Miljević, Milan Nikolić
Извор
International Journal of Molecular Sciences
Издавач
MDPI AG
Датум издавања
2023
Сажетак
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 investi gated 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.
том
24
Број
10
doi
10.3390/ijms24108921
issn
1422-0067
Subject
Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis
Шира категорија рада
M20
Ужа категорија рада
М21
Права
Затворени приступ
Лиценца
Creative Commons – Attribution-No Derivative Works 4.0 International
Формат
.pdf

Lena Platanić Arizanović, Nikola Gligorijević, Ilija Cvijetić, Aleksandar Mijatović, Maja Krstić Ristivojević, Simeon Minić, Aleksandra Nikolić Kokić, Čedo Miljević, Milan Nikolić. "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?" in International Journal of Molecular Sciences, MDPI AG (2023). https://doi.org/10.3390/ijms24108921

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