Spectroscopic, voltammetry and molecular docking study of binding interaction of antipsychotic drug with bovine serum albumin (original) (raw)
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Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019
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 K d values of 9.5 and 172.6 mM. F€ orster 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 a-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.
Journal of Luminescence, 2011
The interaction between promethazine hydrochloride (PMT) and bovine serum albumin (BSA) in vitro was investigated by means of fluorescence spectroscopy and absorption spectroscopy. The fluorescence of BSA was quenched remarkably by PMT and the quenching mechanism was considered as static quenching by forming a complex. The association constants K a and the number of binding sites n were calculated at different temperatures. The BSA-PMT binding distance was determined to be less than 8 nm, suggesting that energy transfer from BSA to PMT may occur. The thermodynamic parameters of the interaction between PMT and BSA were measured according to the van't Hoff equation. The enthalpy change (DH) and entropy change (DS) were calculated to be À 23.62 kJ mol À 1 and À 0.10 J mol À 1 K À 1 , respectively, which indicated that the interaction of PMT with BSA was driven mainly by van der Waals forces and hydrogen bonds. The binding process was a spontaneous process in which Gibbs free energy change (DG) was negative. In addition, the results of synchronous fluorescence spectra and three-dimensional fluorescence spectra showed that binding of PMT with BSA can induce conformational changes in BSA.
Interaction of haloperidol with human serum albumin and effect of metal ions on the binding
Monatshefte für Chemie - Chemical Monthly, 2018
The interaction between human serum albumin (HSA) and haloperidol (HPD) was studied by fluorescence and absorption spectroscopy and molecular modeling under physiological conditions. Fluorescence spectroscopic data showed that the fluorescence quenching of HSA was a result of the formation of the HPD-HSA complex. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of human serum albumin by haloperidol shows a dynamic quenching. The binding constant (K) and the binding sites (n) between haloperidol and HSA were estimated to be 7.94 × 10 3 dm 3 mol −1 and 1.12 at 298 K. The results of thermodynamic parameters, ΔH (− 89.56 kJ mol −1), ΔS (225.94 J mol −1 K −1) and ΔG (− 15.69 kJ mol −1), indicated that the binding process was spontaneous and the van der Waals interactions and hydrogen bonds were the main forces to stabilize the complex. The distance between the donor (HSA) and acceptor (HPD) molecules was obtained according to Förster energy transfer. The effects of metal ions (Ca 2+ , Mg 2+ , Cu 2+ , and Fe 3+) on the binding constant of the haloperidol-HSA complex were also investigated. Finally, the binding of haloperidol to HSA was modeled using the molecular docking method. Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters.
Molecules
Quetiapine (QTP) is a short-acting atypical antipsychotic drug that treats schizophrenia or manic episodes of bipolar disorder. Human serum albumin (HSA) is an essential transport protein that transports hormones and various other ligands to their intended site of action. The interactions of QTP with HSA and their binding mechanism in the HSA-QTP system was studied using spectroscopic and molecular docking techniques. The UV-Vis absorption study shows hyperchromicity in the spectra of HSA on the addition of QTP, suggesting the complex formation and interactions between QTP and HSA. The results of intrinsic fluorescence indicate that QTP quenched the fluorescence of HSA and confirmed the complex formation between HSA and QTP, and this quenching mechanism was a static one. Thermodynamic analysis of the HSA-QTP system confirms the involvement of hydrophobic forces, and this complex formation is spontaneous. The competitive displacement and molecular docking experiments demonstrated tha...
Studies on Binding of Widely used Drugs with Human Serum Albumin at Different Temperatures and PHs
Journal of Biomedical Sciencies, 2016
The study on the interaction of human serum albumin (HSA) with three widely used drugs (diclofenac sodium (DIC), furosemide (FUR) and dexamethasone phosphate (DEX)) was investigated by fluorescence method. Fluorescence emission spectra of HSA in presence of the studied drugs was recorded at excitation wavelength 278 nm and showed that the studied drugs act as quenchers. A decrease in fluorescence emission at 340 nm was attributed to changes in environment of the protein fluorophore caused due to presence of the ligand.
The binding characteristics of human serum albumin (HSA) with N-alkyl phenothiazines derivatives (NAP) viz., levomepromazine monomaleate (LMM) and propericiazine (PPC) have been studied by employing fluorescence, absorption, circular dichroism and FT-IR techniques. The Stern-Volmer quenching constant, K SV values were found to decrease with increase in temperature thereby indicating the presence of static quenching mechanism in the interactions of NAP with HSA. The number of binding sites, n and the binding constant, K were noticed to be, respectively, 1.11 and (5.188 ± 0.034) × 10 4 M −1 for LMM and 1.06 and (4.436 ± 0.066) × 10 4 M −1 for PPC at 298 K. The negative value of enthalpy change and positive value of entropy change in the present study indicated that the hydrophobic forces played a major role in the binding of NAP to HSA. The circular dichroism and FT-IR spectral data revealed the conformational changes in the structure of protein upon its interaction with NAP. The binding distances and the energy transfer efficiency between NAP and protein were determined based on Förster's theory of energy transfer. The decreased binding constants of HAS-LMM and HAS-PPC systems in presence of common ions indicated the availability of higher concentration of free drug in plasma.
Herein we report the interaction of amphiphilic drug clomipramine hydrochloride (CLP-a tricyclic antidepressant) with bovine serum albumin (BSA) studied by fluorescence, UV-vis, and circular dichroism (CD) spectroscopic techniques. Clomipramine hydrochloride is used to treat a variety of mental health problems. The quenching rate constant (k q ) values, calculated according to the fluorescence data, decrease with increase in temperature indicating the static quenching procedure for the CLP-BSA interaction. The association binding constants (K A ), evaluated at different conditions, and the thermodynamic parameters (free energy, enthalpy and entropy changes) indicate that the hydrophobic forces play a major role in the binding interaction of drug. The interaction of BSA with CLP was further confirmed by UV absorption spectra. Blue shift of position was detected due to the complex formation between the BSA-CLP. The molecular distance, r 0 , between donor (BSA) and acceptor (CLP) was estimated by fluorescence resonance energy transfer (FRET) whose value (4.47 nm) suggests high probability of static quenching interaction. The CD results prove the conformational changes in the BSA on binding with the drug. Thus, the results supply qualitative and quantitative understanding of the binding of BSA to CLP, which is important in understanding their effect as therapeutic agents.
Binding of several benzodiazepines to bovine serum albumin: Fluorescence study
Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy, 2010
The interactions of lorazepam, oxazepam and bromazepam with bovine serum albumin (BSA) were studied by fluorescence spectrometry. The Stern–Volmer quenching constants and corresponding thermodynamic parameters ΔH, ΔG and ΔS were calculated. The binding constants and the number of binding sites were also investigated. The distances between the donor (BSA) and the acceptors (benzodiazepines) were obtained according to fluorescence resonance energy
Spectroscopic studies on the binding of bioactive phenothiazine compounds to human serum albumin
In this paper, the binding characteristics of human serum albumin (HSA) with phenothiazine derivatives (PDS) viz., thioridazine hydrochloride (TDH) and triflupromazine hydrochloride (TFP) have been studied by employing different spectroscopic techniques. The Stern-Volmer quenching constant values were found to decrease with increase in temperature thereby indicating the presence of static quenching mechanism in the interactions of PDS with HSA. The number of binding sites, n and the binding constant values, K were noticed to be 1.063 and (4.46 ± 0.040) × 10 4 L M −1 for TDH and 1.08 and (5.18 ± 0.071) × 10 4 L M −1 for TFP, respectively at 298 K. The binding distances and the energy transfer efficiency between PDS and protein were determined. The negative value of enthalpy change and positive value of entropy change in the present study indicated that both hydrogen bonding and hydrophobic forces played a major role in the binding of PDS to HSA. The circular dichroism data revealed the conformational changes in secondary structure of protein upon its interaction with PDS. The decreased binding constants of HSA-TDH/TFP in presence of common ions indicated the availability of higher concentration of free drug in plasma.
Journal of Spectroscopy
In this research, the pyrazoline pyridazine derivative 7-methyl-2-phenyl-4-(3,4,5-trimethoxyphenyl)-2H-pyrazolo[3,4-d]pyridazine (5d) was studied for its interaction with bovine serum albumin (BSA). Various spectroscopic techniques along with molecular docking analysis were utilized to understand the mechanism of interaction. The quenching of BSA fluorescence by using investigational drug 5d was the basic principle for the methodology. Spectrofluorometric methods and UV-absorption studies were conducted for exploration of the 5d and BSA binding mechanism. The fluorescence quenching mechanism involved in BSA and 5d interaction was static quenching, and a complex formation also occurred between them. Both enthalpy and entropy attained positive values suggesting involvement of hydrophobic forces in BSA and 5d interaction. The Förster distance of 2.23 nm was calculated by fluorescence resonance energy transfer (FRET). An alteration in BSA secondary structure was proven from the conforma...