Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
Abstract
:1. Introduction
2. Results and Discussion
2.1. Fluorescence Quenching of Human Hemoglobin by Atypical Antipsychotics
2.2. Binding Constants Determination in Human Hemoglobin and Antipsychotic Systems
2.3. Synchronous Fluorescence Measurements in Human Hemoglobin and Antipsychotic Systems
2.4. Thermodynamic Study of Antipsychotics Binding to Human Hemoglobin
2.5. Docking Results
2.6. Circular Dichroism Spectra Analysis
2.7. Effect of Atypical Antipsychotics on the Thermal Stability of Human Hemoglobin
2.8. Effect of Atypical Antipsychotics on Spontaneous Human Hemoglobin Oxidation
2.9. Effect of Atypical Antipsychotics on Oxidant-Assisted Human Hemoglobin Oxidation
3. Materials and Methods
3.1. Materials
3.2. Methods
3.2.1. Fluorescence Measurements
3.2.2. Circular Dichroism (CD) Measurements
3.2.3. Visible Absorbance (Vis) Measurements
3.2.4. Statistical Analysis
3.2.5. Molecular Docking
3.3. Theory and Calculations
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ligand | T (K) | KSV (M−1) | R2 | Kq (M−1 s−1) |
---|---|---|---|---|
298.15 | 2.22 × 103 | 0.9958 | 2.22 × 1011 | |
Clozapine | 303.15 | 2.01 × 103 | 0.9957 | 2.01 × 1011 |
310.15 | 1.84 × 103 | 0.9952 | 1.84 × 1011 | |
298.15 | 0.67 × 103 | 0.9956 | 0.67 × 1011 | |
Ziprasidone | 303.15 | 0.62 × 103 | 0.9957 | 0.62 × 1011 |
310.15 | 0.55 × 103 | 0.9970 | 0.55 × 1011 | |
298.15 | 2.71 × 103 | 0.9981 | 2.71 × 1011 | |
Sertindole | 303.15 | 2.29 × 103 | 0.9957 | 2.29 × 1011 |
310.15 | 1.16 × 103 | 0.9911 | 1.16 × 1011 |
Ligand | T (K) | Ka × 104 (M−1) | n | ΔG (kJ mol−1) | ΔS (J mol−1 K−1) | ΔH (kJ mol−1) |
---|---|---|---|---|---|---|
298.15 | 2.19 | 1.12 | −12.2 | |||
Clozapine | 303.15 | 2.03 | 1.03 | −12.4 | +41.0 | −12.5 |
310.15 | 1.80 | 0.97 | −12.7 | |||
298.15 | 0.74 | 1.16 | −12.3 | |||
Ziprasidone | 303.15 | 0.69 | 1.08 | −12.5 | +41.2 | −9.8 |
310.15 | 0.63 | 1.06 | −12.8 | |||
298.15 | 1.81 | 1.10 | −16.9 | |||
Sertindole | 303.15 | 1.71 | 1.06 | −17.2 | +56.8 | −7.4 |
310.15 | 1.61 | 1.03 | −17.6 |
Sample & Monitored Parameter | α-Helices Content (%) | metHHb Content (%) | Protection from Oxidation (AU) |
---|---|---|---|
Control HHb (4 µM) | 48.2 ± 0.7 | 3.96 ± 0.20 | 1 (reference) |
+clozapine (10 µM) | 52.2 ± 0.5 a | 3.86 ± 0.23 | 118 ± 4.1 |
+ziprasidone (10 µM) | 50.2 ± 0.6 | 5.32 ± 0.27 c | 78 ± 3.2 |
+sertindole (10 µM) | 49.9 ± 1.0 | 5.14 ± 0.42 b | 60 ± 2.8 |
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Platanić Arizanović, L.; Gligorijević, N.; Cvijetić, I.; Mijatović, A.; Ristivojević, M.K.; Minić, S.; Kokić, A.N.; Miljević, Č.; Nikolić, M. Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes? Int. J. Mol. Sci. 2023, 24, 8921. https://doi.org/10.3390/ijms24108921
Platanić Arizanović L, Gligorijević N, Cvijetić I, Mijatović A, Ristivojević MK, Minić S, Kokić AN, Miljević Č, Nikolić M. Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes? International Journal of Molecular Sciences. 2023; 24(10):8921. https://doi.org/10.3390/ijms24108921
Chicago/Turabian StylePlatanić Arizanović, Lena, Nikola Gligorijević, Ilija Cvijetić, Aleksandar Mijatović, Maja Krstić Ristivojević, Simeon Minić, Aleksandra Nikolić Kokić, Čedo Miljević, and Milan Nikolić. 2023. "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?" International Journal of Molecular Sciences 24, no. 10: 8921. https://doi.org/10.3390/ijms24108921