ABSTRACT
Tenofovir (TFR) is an antiviral drug commonly used to fight against viral diseases infection due to its good potency and high genetic barrier to drug resistance. In physiological conditions, TFR is less water soluble, more unstable, and less permeable, limiting its effective therapeutic applications. In addition to their use in treating the Coronavirus disease 2019 (COVID-19), cyclodextrins (CDs) are also being used as a molecule to develop therapies for other diseases due to its enhance solubility and stability. This study is designed to synthesize and characterization of ß-CD:TFR inclusion complex and its interaction against SARS-CoV-2 (MPro) protein (PDB ID;7cam). Several techniques were used to characterize the prepared ß-CD:TFR inclusion complex, including UV-Visible, FT-IR, XRD, SEM, TGA, and DSC, which provided appropriate evidence to confirm the formation. A 1:1 stoichiometry was determined for ß-CD:TFR inclusion complex in aqueous medium from UV-Visible absorption spectra by using the Benesi-Hildebrand method. Phase solubility studies proposed that ß-CD enhanced the excellent solubility of TFR and the stability constant was obtained at 863 ± 32 M-1. Moreover, the molecular docking confirmed the experimental results demonstrated the most desirable mode of TFR encapsulated into the ß-CD nanocavity via hydrophobic interactions and possible hydrogen bonds. Moreover, TFR was validated in the ß-CD:TFR inclusion complex as potential inhibitors against SARS-CoV-2 main protease (Mpro) receptors by using in silico methods. The enhanced solubility, stability, and antiviral activity against SARS-CoV-2 (MPro) suggest that ß-CD:TFR inclusion complexes can be further used as feasible water-insoluble antiviral drug carriers in viral disease infection.
ABSTRACT
An innovative sonication method has been developed to produce inclusion complexes (ICs) of Oseltamivir (OTV) which is a potentially water-soluble anti-viral agent with lesser cytotoxicity. Proton signals and chemical shifts of OTV without any ambiguity confirm the formation of ICs with β-Cyclodextrin (B-CD) and Hydroxypropyl-β-cyclodextrin (H-CD). ICs are also supported by their atomic percentages as secondary evidence using XPS analysis. Analysis of drug release at three pH levels revealed the slow release of the OTV from ICs and also suitable for viral inactivation. A very less cytotoxic ability on cancer cell lines and enhanced the viral inactivation of OTV after being made into water-soluble ICs. © 2022 Elsevier B.V.
ABSTRACT
Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/ßCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet-visible absorption (UV-vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC-MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job's plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of ß-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the ß-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/ßCD inclusion complex has both -2S and -2R stereoisomers of hesperetin-7-O-glucoside possibly in the -2S/-2R epimeric ratio of 1/1.43 (i.e., -2S: 41.1% and -2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in ß-CD is complete inclusion, wherein both ends of HEPT7G are included in the ß-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with ß-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.
Subject(s)
Hesperidin , beta-Cyclodextrins , Calorimetry, Differential Scanning , Flavonoids/chemistry , Glucosides , Protons , Solubility , Spectroscopy, Fourier Transform Infrared/methods , X-Ray Diffraction , beta-Cyclodextrins/chemistryABSTRACT
During the current outbreak of the novel coronavirus disease 2019 (COVID-19), researchers have examined several antiviral drugs with the potential to inhibit the proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antiviral drug acyclovir (AVR), which is used to treat COVID-19, in complex with methyl-ß-cyclodextrin (Mß-CD) was examined in the solution and solid phases. UV-visible and fluorescence spectroscopic analyses confirmed that the guest (AVR) was included inside the host (Mß-CD) cavity. A solid inclusion complex of AVR was prepared by co-precipitation, physical mixing, kneading, and bath sonication methods at a 1:1 ratio of Mß-CD:AVR. The prepared Mß-CD:AVR inclusion complex was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis. Phase solubility studies indicated the Mß-CD:AVR inclusion complex exhibited a higher stability constant and linear enhancement in AVR solubility with increasing Mß-CD concentrations. In silico analysis of the Mß-CD/AVR inclusion complex confirmed that AVR drugs show potential as inhibitors of SARS-CoV-2 3C-like protease (3CLpro) receptors. Results obtained using the PatchDock and FireDock servers indicated that the most favorable docking ligand was Mß-CD:AVR, which interacted with SARS-CoV-2 (3CLPro) protease inhibitors with high geometric shape complementarity scores (2522 and 5872) and atomic contact energy (-313.77 and -214.70 kcal mol-1). Our results suggest that the Mß-CD/AVR inclusion complex inhibits the main protease of SARS-CoV-2, although further wet-lab experiments are needed to verify these findings.
ABSTRACT
This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-ß-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-ß-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-ß-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het.