Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study

Abstract

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (Kb) of 1.69 ± 0.15 × 103 M−1 at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal’s interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

Effects of PPAR‐γ agonists on oral cancer cell lines: Potential horizons for chemopreventives and adjunctive therapies

“…In experiments using 0%, 2.5%, and 5% serum‐containing media, the growth inhibiting effects of each treatment were decreased in the presence of increasing concentrations of serum‐containing media (Figure 2A‐D). These findings confirm oral cancer cells benefit from the presence of serum in the culture media, either from serum binding of drug or other cytoprotection afforded by serum, consistent with published data utilizing varying concentrations of serum‐containing media, as well as serum‐free media 22,23 . Further, this indicates increased serum concentrations of either agent might be necessary in vivo.…”

“…These findings confirm oral cancer cells benefit from the presence of serum in the culture media, either from serum binding of drug or other cytoprotection afforded by serum, consistent with published data utilizing varying concentrations of serum-containing media, as well as serum-free media. 22,23 Further, this indicates increased serum concentrations of either agent might be necessary in vivo.…”

Kanamycin-Mediated Conformational Dynamics of Escherichia coli Outer Membrane Protein TolC

“…The raw data obtained for kanamycin and TolC interaction was fitted to the binding models using the inbuilt origin software. The negative values of Gibb's free energy indicates the spontaneous formation of the TolC-kanamycin complex (Rahman et al, 2019). The best fitted ITC isotherm shows a single binding site model and the thermodynamic parameters obtained are listed below in Table 2.…”

Structural and inhibitory effects of fulvic and humic acids against tyrosinase

“…Utilizing K A , the absolute temperature (T), and the universal gas con- The magnitudes of ΔG° were calculated at both temperatures for HA and FA (Table 1). The negative values of ΔG° indicate that the binding of HA or FA to tyrosinase was spontaneous (Rahman et al, 2019). Employing Van't Hoff equation (Equation 8), the values of entropy change (ΔS°) and enthalpy change (ΔH°) were determined (Hekmat & Saboury, 2019).…”