Supramolecular interactions between β‐lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling

Abstract

Supramolecular interactions between β-lapachone (β-lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X-ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT-IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed β-, HP-β-, SBE-β-, γ-, and HP-γ-CDs at 1.5% (w/w) allowed an increase in apparent solubility of β-lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. β-lap has a weak interaction with γ- and HP-γ-CDs and tends to interact more favorably with β-CD and its derivatives, especially SBE-β-CD (K = 4160 M ; ΔG = -20.66 kJ·mol ). Thermodynamic analysis suggests a hydrophobic interaction associated with the displacement of water from the cavity of the CD by the β-lap. In addition, van der Waals forces and hydrogen bonds were responsible for the formation of complexes. Taken together, the results showed intermolecular interactions between β-lap and SBE-β-CD, thereby confirming the formation of the inclusion complex. Molecular docking results showed 2 main orientations in which the interaction of benzene moiety at the wider rim of the SBE-β-CD is the most stable (average docking energy of -7.0 kcal/mol). In conclusion, β-lap:SBE-β-CD is proposed as an approach for use in drug delivery systems in cancer research.

Stereochemistry and amyloid inhibition: Asymmetric triplex metallohelices enantioselectively bind to Aβ peptide

“…The binding was exothermic according to the net enthalpy change (fig. S9) ( 37 ) and gave the best fit to 1:1 binding. The thermodynamic parameters were summarized in table S3, including the binding constant ( K a ), enthalpy change (Δ H ), entropy change (Δ S ), and Gibbs free energy change (Δ G ) upon the interaction between Aβ and metallohelices.…”

Thermodynamic Studies of Interactions between Sertraline Hydrochloride and Randomly Methylated β-Cyclodextrin Molecules Supported by Circular Dichroism Spectroscopy and Molecular Docking Results

“…The aim of presented work was to obtain information about interactions of sertraline hydrochloride (SRT) (Figure 1a) with randomly methylated β-cyclodextrin (RMβCD) (Figure 1b) in water solutions at 298.15 K under atmospheric pressure. The binding process of guest molecule with cyclodextrin was examined with the use of an isothermal titration calorimetry (ITC) [43][44][45] and molecular docking studies (MD) [10,43,45]. The outcome was compared with the set of data for other complexes of SRT with non-ionic β-cyclodextrin derivatives (Figure 1b) received from the literature [31,41,42].…”

Estudo in Silico De Complexos De Inclusão Com Ciclodextrinas Para Incremento De Solubilidade Dacantin-6-Ona

“…Nesse caso, o host seria a CD (ou seu derivado) e o guest seria um fármaco (ou uma molécula bioativa), formando o complexo host-guest DUCHÊNE, 2007). Os estudos de modelagem molecular estão presentes na maioria dos trabalhos envolvendo as CDs ou seus derivados, normalmente com o objetivo de elucidar as interações intermoleculares que estabilizam a formação do complexo host-guest (SILVA et al, 2016;XAVIER-JUNIOR et al, 2017).…”