Interaction between carisoprodol and bovine serum albumin and effect of β-cyclodextrin on binding: insights from molecular docking and spectroscopic techniques

Abstract

Biomolecular interaction of carisoprodol (CAP) with bovine serum albumin (BSA) has been studied by fluorescence and UV-visible spectroscopy and confirmed by multispectroscopic methods including molecular docking studies. The intrinsic intensity of BSA was quenched by dynamic quenching mechanism. The binding constant and number of binding sites were calculated according to Stern-Volmer equation. Effect of β-Cyclodextrin on the binding has been studied. Thermodynamic parameters were calculated which reveal the involvement of hydrophobic interactions in the binding. Based on the Fӧrster's theory of non-radiation energy transfer, the average binding distance(r) between BSA and CAP was evaluated. Spectral results showed that the binding of CAP to BSA induced conformational changes in BSA. Molecular docking study confirms the drug binding sites and interaction of CAP with amino acid residues. 2 protein. Therapeutic effectiveness of drugs depends on their binding ability and the extent of binding of the drug to the organism.Carisoprodol (N-isopropyl-2 methyl-2-propyl-1, 3-propanediol dicarbamate) is a centrally acting muscle relaxant drug for acute painful musculoskeletal treatments (Fig. 1A). 1 Upon being ingested and metabolized, drugs can have ability to form substances called metabolites.Similarly, carisoprodol is metabolized to a pharmacologically active compound meprobamate which is indicated for the treatment of anxiety. 2 The pharmacological effects of carisoprodol is due to the combination of the effects of carisoprodol and meprobamate. In addition to the desired skeletal muscle-relaxing effects, carisoprodol and meprobamate also produce weak anticholinergic, antipyretic, and analgesic effects. 3 Serum albumins are the most abundant plasma proteins found in the circulatory system of wide veriety of organisms. 4 Bovine serum albumin (BSA) consists of three linearly arranged domains (I-III) that are composed of two subdomains (A and B) ( Fig. 1(B)). 5 There are two tryptophan residues (Trp134 and Trp213), of which Trp134 is located on the surface of the molecule and Trp213 resides in the hydrophobic pocket. There is evidence of conformational changes of serum albumin induced by its interaction with low molecular weight dyes and drugs, which appear to affect secondary and tertiary structures of proteins. 6 β-Cyclodextrin (β-CD), is composed of seven units of D(+)-glucopyranose units joined by α-1, 4-glycosidic bonds arranged in a truncated cone-shaped structure. 7 As one of the water-soluble cyclic oligosaccharides, it can form inclusion complexes with a large variety of organic and inorganic compounds, which may improve the solubility, stability and bioavailability of guest molecules. As a result, β-CD has been widely applied in food research, organic synthesis, environment protection and especially in the area of pharmacological science. 8 β-Cyclodextrins are used as additives with drugs (mixed with drug solution) to improve their stability, solubility and cover up the smell of medicine.

Site-Selective Interaction of Human Serum Albumin with 4-Chloro-7-nitro-1,2,3-benzoxadiazole Modified Olanzapine Derivative and Effect of β-Cyclodextrin on Binding: In the Light of Spectroscopy and Molecular Docking

“…The smaller K SV and K b values in the presence of β-CD for the HSA−OLA-NBD binding association indicate that β-CD prevents the direct collision of OLA-NBD molecules with HSA by forming an inclusion complex. 62,63 It also implies that OLA-NBD molecules are progressively unsheathed from β-CD by HSA to accomplish its medicinal outcome upon binding with protein. 58,62−64 HSA−OLA-NBD Association Kinetics.…”

“…The calculated K SV and K b values from Figures S10 and S11, respectively, at 25 °C in the absence and presence of β-CD are summarized in Table . The smaller K SV and K b values in the presence of β-CD for the HSA–OLA-NBD binding association indicate that β-CD prevents the direct collision of OLA-NBD molecules with HSA by forming an inclusion complex. , It also implies that OLA-NBD molecules are progressively unsheathed from β-CD by HSA to accomplish its medicinal outcome upon binding with protein. ,− …”

In Vitro Investigation on Behavior of Pyriproxyfen Binding onto Bovine Serum Albumin by Mean of Various Spectroscopic Methodologies and In Silico

“…3D fluorescence spectra of BSA upon adding PPF were shown in Figure . The results represented that there are three emission peaks: Rayleigh Scattering peak ( λ ex = λ em ), the emission peak of Trp and Tyr, and second order scattering peak (2 λ ex = λ em ) . Obviously, the intensity of emission peak for BSA solution (1.0 μM) gradually declined from 550.3 a.u.…”

Three Pt(ii) complexes based on thiosemicarbazone: synthesis, HSA interaction, cytotoxicity, apoptosis and cell cycle arrest

“…It is reported that synchronous uorescence spectroscopy is frequently used to characterize the interaction between the uorescent probe and proteins, 30 because it is of great importance for providing information about the molecular environment around the uorophore molecules. 31 The synchronous uorescence spectroscopy performs the simultaneous scanning of excitation and emission spectra on a uorimeter, and xes the wavelength difference (Dl) between them. When Dl is stabilized at 15 nm, the synchronous uorescence represents the state of tyrosine residues, whereas Dl of 60 nm indicates that of tryptophan residues.…”