Characterizing the interactions of the antipsychotic drug trifluoperazine with bovine serum albumin: Probing the drug-protein and drug-drug interactions using multi-spectroscopic approaches.
Spectrochim Acta A Mol Biomol Spectrosc
; 226: 117584, 2020 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-31698317
ABSTRACT
Trifluoperazine is a potent antipsychotic drug used in the treatment of neurological disorders. The usage of trifluoperazine is often found to be associated with more adverse side effects as compared to other low-potency antipsychotic agents. Plasma proteins play an inevitable role in determining the pharmacokinetic properties of a drug. Hence, this study was conducted with an aim to characterize the interactions of trifluoperazine with bovine serum albumin and determine the influence of other small molecules on its interaction with serum albumin. Trifluoperazine bound to BSA at two independent sites with Kd values of 9.5 and 172.6⯵M. Förster resonance energy transfer and computational docking analysis revealed that both the binding sites of trifluoperazine were located closer to TRP 213 in subdomain IIA of BSA. Evaluation of trifluoperazine-BSA interactions at three different temperatures indicated that there was a stable complex formation between the two molecules at the ground state and that the static quenching mechanism was predominant behind these interactions. Binding studies in the presence of pharmaceutically relevant drugs indicated that warfarin, paracetamol, and caffeine negatively influenced the binding of trifluoperazine on BSA. Lastly, Fourier transformed infrared spectroscopy and circular dichroism spectroscopy indicated that the binding of trifluoperazine induced a conformational change by reducing the α-helical content of BSA. The study implicates that the small molecules which prefer binding to the Sudlow site I of BSA might compete with trifluoperazine for its binding site thereby increasing the concentration of free trifluoperazine in the plasma which could lead to adverse side effects in patients.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trifluoperazina
/
Albúmina Sérica Bovina
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Simulación del Acoplamiento Molecular
Límite:
Animals
Idioma:
En
Revista:
Spectrochim Acta A Mol Biomol Spectrosc
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
India