Enhanced solubility of galangin based on the complexation with methylated microbial cyclosophoraoses

Abstract

Methylated cyclosophoraoses (M-Cys) were synthesized by reaction using dimethyl sulfate with native Cys (unbranched cyclic b-1,2-D-glucans) isolated from Rhizobium leguminosarum biovar viciae VF-39. Its structure was proven using nuclear magnetic resonance ( 1 H NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Based on the enhanced hydrophobicity by methylation of Cys, we investigated the inclusion property with the water-insoluble flavonoid, galangin, through a phase solubility study using ultraviolet-visible spectroscopy. The solubility of galangin was enhanced 5.6-fold according to the added concentrations (1 mM) of M-Cys, compared to the 1.9-fold and 3.4-fold enhancements by b-Cyclodextrin (b-CD) and heptakis (2,6-di-O-methyl)-b-cyclodextrin (DM-b-CD), respectively. M-Cys was also shown to have the highest binding constant (5,534 M -1 ) with galangin among the tested host molecules (b-CD, DM-b-CD, Cys, and M-Cys). From this result, we can infer that the complex of galangin with M-Cys is more stable than any of the other host molecules. The continuous variation method showed that the galangin/M-Cys complex was suitable for 1:1 stoichiometry. The formation of the complex was confirmed with 1 H NMR, FT-IR, differential scanning calorimetry, and scanning electron microscopy. Furthermore, the hypothetical molecular model of 1:1 galangin/M-Cys complex was suggested by molecular docking simulations. The cytotoxicity to the human cervical adenocarcinoma cell lines was enhanced by the galangin/M-Cys complex compared with free galangin. The obtained results indicate that M-Cys can be utilized as an effective complexing agent for galangin.

Properties and current applications of bacterial cyclic β-glucans and their derivatives

“…In the case of uncharged derivatives, methylated cyclic b-(1,2) glucans were synthesized by the reaction of the original glucans, potassium hydroxide and dimethyl sulfate in anhydrous tetrahydrofuran [29]. By doing so, the hydrophobicity of host could be enhanced, and the changed characteristics contributed to the differentiated complexation results.…”

“…Then, various modified structures such as carboxymethyl, butyryl, succinyl, and methyl derivatives have also been utilized as shown in Table 1, and in particular hydroxyl modifications show the successful solubility enhancement on relatively large non-polar drugs such as polycyclic aromatic hydrocarbons and anaphtoflavone [30,104]. The bioavailability enhancement is also shown via increasing the solubility or stability [29,105]. For the use of biomedical application, cyclic b-(1,2) glucans have shown no hemolytic effects on human erythrocytes, no toxicity and no immunogenicity [20,61].…”

“…In fact, various bulky compounds such as amphotericin B, paclitaxel, indomethacin, reserpine, steroids, and vitamins have formed inclusion complexes with cyclic b-(1,2) glucans [22][23][24][25][26]. Recent study has also shown some results induced by the complexing ability of cyclic b-(1,3)-b-(1,6) and cyclic b-(1,2)-a-(1,6) glucans as well as the chemically derivatized cyclic b-(1,2) glucans [27][28][29][30][31].…”

Oil-based cyclo-oligosaccharide nanodevices for drug encapsulation

“…The chemical modification of Cys has been also assessed by Kim et al, to increase its hydrophobicity [20]. Their studies revealed the improvement of the solubility of insoluble flavonoids, comparing with the non-modified Cys [20].…”

Synthesis of Microbial Cyclosophoraose Derivatives Grafted Magnetic Nanoparticles

“…To increase the variety of molecules with which they can interact, Cys have been chemically modified with functional moieties such as butyryl, methyl, and carboxymethyl groups. [5][6][7] The modifications enhance the ability of Cys to form complexes with flavonoids, hydrobenzoin, and N-acetyltryptophan, as compared to that of the unmodified Cys. Carboxymethylated Cys enhanced the solubility of hydrobenzoin, and N-acetyltryptophan about 5.1-and 299-fold, respectively.…”