Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Methylated cyclosophoraoses (M-Cys) were synthesized by reaction using dimethyl sulfate with native Cys (unbranched cyclic β-1,2-d-glucans) isolated from Rhizobium leguminosarum biovar viciae VF-39. Its structure was proven using nuclear magnetic resonance (1H 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 β-Cyclodextrin (β-CD) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), respectively. M-Cys was also shown to have the highest binding constant (5,534 M−1) with galangin among the tested host molecules (β-CD, DM-β-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 1H 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

Cys:

Cyclosophoraoses

M-Cys:

Methylated cyclosophoraoses

β-CD:

β-Cyclodextrin

DM-β-CD:

Heptakis (2,6-di-O-methyl)-β-Cyclodextrin

MALDI-TOF MS:

Matrix assisted laser desorption/ionization time-of-flight mass spectrometry

1H NMR:

1H nuclear magnetic resonance

FT-IR:

Fourier-transform infrared spectroscopy

UV–Vis:

Ultraviolet-visible

DSC:

Differential scanning calorimetry

SEM:

Scanning electron microscopy

DP:

Degree of polymerization

TLC:

Thin layer chromatography

DS:

Degree of substitution

D2O:

Deuterium oxide

DMSO:

Dimethyl sulfoxide-d6

DHB:

2,5-Dihydroxybenzoic acid

MW:

Molecular weight

References

  1. Abe, M., Amemura, A., Higashi, S.: Studies on cyclic beta-l,2- glucan obtained from periplasmic space of Rhizobium trifolii cells. Plant Soil 64, 315–324 (1982)

    Article  CAS  Google Scholar 

  2. Amemura, A., Hisamatsu, M., Mitani, H., Harada, T.: Cyclic (1 → 2)-b-d-glucan and the octasaccharide repeating-units of extracellular acidic polysaccharides produced by Rhizobium. Carbohydr. Res. 114, 277–285 (1983)

    Article  CAS  Google Scholar 

  3. Miller, K.J., Kennedy, E.P., Reinhold, V.N.: Osmotic adaptation by gram-negative bacteria: possible role for periplasmic oligosaccharides. Science 231, 48–51 (1986)

    Article  CAS  Google Scholar 

  4. Zorreguieta, A., Cavaignac, S., Geremia, R.A., Ugalde, R.A.: Osmotic regulation of beta(1–2) glucan synthesis in members of the family Rhizobiaceae. J. Bacteriol. 172, 4701–4704 (1990)

    CAS  Google Scholar 

  5. Leighand, J.L., Coplin, D.L.: Exopolysaccharides in plant-bacterial interactions. Annu. Rev. Microbiol. 46, 307–346 (1992)

    Article  Google Scholar 

  6. Lee, S., Jung, S.: Enantioseparation using cyclosophoraoses as a novel chiral additive in capillary electrophoresis. Carbohydr. Res. 338, 1143–2246 (2003)

    Article  CAS  Google Scholar 

  7. Jung, Y., Lee, S., Paik, S.R., Jung, S.: Cyclosophoraose as a novel chiral stationary phase for enantioseparation. J. Microbiol. Biotechnol. 14, 1338–1342 (2004)

    CAS  Google Scholar 

  8. Park, H., Kang, L., Jung, S.: Methanolysis of 7-acetoxy-4-methylcoumarin catalyzed by cyclosophoraoses isolated from Rhizobium meliloti. Bull. Korean Chem. Soc. 29, 228–230 (2008)

    Article  CAS  Google Scholar 

  9. Park, H., Jung, S.: Methanolysis of ethyl esters of N-acetyl amino acids catalyzed by cyclosophoraoses isolated from Rhizobium meliloti. Carbohydr. Res. 343, 274–281 (2008)

    Article  CAS  Google Scholar 

  10. Lee, S., Seo, D., Kim, H., Jung, S.: Investigation of inclusion complexation of paclitaxel by cyclohenicosakis-(1 → 2)-(beta-d-glucopyranosyl), by cyclic-(1 → 2)-beta-d-glucans (cyclosophoraoses), and by cyclomaltoheptaoses (beta-cyclodextrins). Carbohydr. Res. 334, 119–126 (2001)

    Article  CAS  Google Scholar 

  11. Lee, S., Kwon, C., Choi, Y., Seo, D., Kim, H., Jung, S.: Inclusion complexation of a family of cyclosophoraoses with indomethacin. J. Microbiol. Biotechnol. 11, 463–468 (2001)

    CAS  Google Scholar 

  12. Kwon, C., Choi, Y., Kim, N., Yoo, J., Yang, C., Kim, H., Jung, S.: Complex forming ability of a family of isolated cyclosophoraoses with ergosterol and its Monte Carlo docking comutatational analysis. J. Incl. Phenom. 36, 55–65 (2000)

    Article  CAS  Google Scholar 

  13. Koizumi, K., Okada, Y., Horiyama, S., Utamura, T., Higashiura, T., Ikeda, M.: Preparation of cyclosophoraose-A and its complexforming ability. J. Incl. Phenom. 2, 891–899 (1984)

    Article  CAS  Google Scholar 

  14. Lee, S., Seo, D., Park, H., Choi, Y., Jung, S.: Solubility enhancement of a hydrophobic flavonoid, luteolin by the complexation with cyclosophoraoses isolated from Rhizobium meliloti. Antonie Van Leeuwenhoek 84, 201–207 (2003)

    Article  CAS  Google Scholar 

  15. Jeon, Y., Kwon, C., Cho, E., Jung, S.: Carboxymethylated cyclosophoraose as a novel chiral additive for the stereoisomeric separation of some flavonoids by capillary electrophoresis. Carbohydr. Res. 345, 2408–2412 (2010)

    Article  CAS  Google Scholar 

  16. Kwon, C., Choi, Y., Jeong, D., Kim, J.G., Choi, J.M., Chun, S., Park, S., Jung, S.: Inclusion complexation of naproxen with cyclosophoraoses and succinylated cyclosophoraoses in different pH environments. J. Incl. Phenom. 74, 325–333 (2012)

    Article  CAS  Google Scholar 

  17. Park, H., Lee, S., Kang, S., Jung, Y.J., Jung, S.: Enantioseparation using sulfated cyclosophoraoses as a novel chiral additive in capillary electrophoresis. Electrophoresis 25, 2671–2674 (2004)

    Article  CAS  Google Scholar 

  18. Park, H., Choi, Y., Kang, S., Lee, S., Kwon, C., Jung, S.: pH dependent inclusion complexation of carboxymethylated cyclosophoraoses to N-acetyl phenylalanine. Carbohydr. Polym. 64, 85–89 (2006)

    Article  CAS  Google Scholar 

  19. Lee, S., Park, H., Seo, D., Choi, Y., Jung, S.: Synthesis and characterization of carboxymethylated cyclosophoraose, and its inclusion complexation behavior. Carbohydr. Res. 339, 519–527 (2004)

    Article  CAS  Google Scholar 

  20. Kwon, C., Jung, S.: pH-Dependent inclusion complexation of highly succinylated cyclosophoraoses with 4′-hydroxyflavanone. Bull. Korean Chem. Soc. 32, 2991–2994 (2011)

    Google Scholar 

  21. Kwon, Y., Cho, E., Lee, I.S., Jung, S.: Synthesis and characterization of butyryl cyclosophoraose, and its inclusion complexation behavior for some flavonoids. Bull. Korean Chem. Soc. 32, 2779–2782 (2011)

    Article  Google Scholar 

  22. Patel, D.K., Patel, K., Gadewar, M., Tahilyani, V.: Pharmacological and bioanalytical aspects of galangin-a concise report. Asian Pac. J. Trop. Biomed. 2, S449–S455 (2012)

    Article  Google Scholar 

  23. Dufour, C., Dangles, O.: Flavonoid-serum albumin complexation: determination of binding constants and binding sites by fluorescence spectroscopy. Biochim. Biophys. Acta 1721, 164–173 (2005)

    Article  CAS  Google Scholar 

  24. Bergonzi, M.C., Bilia, A.R., Bari, L.D., Mazzia, G., Vincieria, F.F.: Studies on the interactions between some flavonols and cyclodextrins. Bioorg. Med. Chem. Lett. 17, 5744–5748 (2007)

    Article  CAS  Google Scholar 

  25. Øyvind, M.A., Kenneth, R.M.: Flavonoids: Chemistry, Biochemistry, and Applications. CRC, Boca Raton (1994)

    Google Scholar 

  26. Heo, M.Y., Sohn, S.J., Au, W.W.: Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutat. Res. 488, 135–150 (2001)

    Article  CAS  Google Scholar 

  27. Cholbi, M.R., Paya, M., Alcaraz, M.J.: Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid peroxidation. Experientia 47, 195 (1991)

    Article  CAS  Google Scholar 

  28. Jullian, C.: Improvement of galangin solubility using native and derivative cyclodextrins. An UV–Vis and NMR. J. Chil. Chem. Soc. 54, 201–203 (2009)

    Article  CAS  Google Scholar 

  29. Kim, H., Choi, J., Jung, S.: Inclusion complexes of modified cyclodextrins with some flavonols. J. Incl. Phenom. Macrocycl. Chem. 64, 43–47 (2009)

    Article  CAS  Google Scholar 

  30. Jullian, C., Alfaro, M., Torres, G.Z., Azar, C.O.: Inclusion complexes of cyclodextrins with galangin: a Thermodynamic and reactivity study. J. Solution Chem. 39, 1168–1177 (2010)

    Article  CAS  Google Scholar 

  31. Breedveld, M.W., Zevenhuizen, L.P., Zehnder, A.J.: Osmotically-regulated trehalose accumulation and cyclic β-(1,2)-glucan excretion by Rhizobium leguminosarum biovar trifolii TA-1. Arch. Microbiol. 156, 501–506 (1991)

    CAS  Google Scholar 

  32. Breedveld, M.W., Zevenhuizen, L.P., Zehnder, A.J.: Excessive excretion of cyclic β-(1,2)-glucan by Rhizobium trifolii TA-1. Appl. Environ. Microbiol. 56, 2080–2086 (1990)

    CAS  Google Scholar 

  33. Gharbi, A., Humblot, V., Turpin, F., Pradier, C.M., Imbert, C., Berjeaud, J.M.: Elaboration of antibiofilm surfaces functionalized with antifungal-cyclodextrin inclusion complexes. FEMS Immunol. Med. Microbiol. 65, 257–269 (2012)

    Article  CAS  Google Scholar 

  34. Higuchi, T., Connors, K.A.: Phase solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  35. Loftsson, T., Magnúsdóttir, A., Másson, M., Sigurjónsdóttir, J.F.: Self-association and cyclodextrin solubilization of drugs. J. Pharm. Sci. 91, 2307–2316 (2002)

    Article  CAS  Google Scholar 

  36. Martins, M.H., Calderini, A., Pessine, F.B.T.: Host–guest interactions between dapsone and β-cyclodextrin (Part II): thermal analysis, spectroscopic characterization, and solubility studies. J. Incl. Phenom. Macrocycl. Chem. 74, 109–116 (2012)

    Article  CAS  Google Scholar 

  37. Gil, V.M.S., Oiiveira, N.C.: On the use of the method of continuous variations. J. Chem. Educ. 67, 473–478 (1990)

    Article  CAS  Google Scholar 

  38. Hirose, K.: A practical guide for the determination of binding constants. J. Incl. Phenom. Macrocycl. Chem. 39, 193–209 (2001)

    Article  CAS  Google Scholar 

  39. Schneider, H.J., Hacket, F., Rudiger, V., Ikeda, H.: NMR studies of cyclodextrins and cyclodextrin complexes. Chem. Rev. 98, 1755–1786 (1998)

    Article  CAS  Google Scholar 

  40. Gibaud, S., Zirar, S.B., Mutzenhardt, P., Fries, I., Astier, A.: Melarsoprol–cyclodextrins inclusion complexes. Int. J. Pharm. 306, 107–121 (2005)

    Article  CAS  Google Scholar 

  41. Stancic-rotaru, M., Mititelu, M., Crasmaru, M., Balaban, D.: Spectroanalytical profile of flavonoids from Chelidonium majus L. Rom. Biotechnol. Lett. 8, 1093–1100 (2003)

    CAS  Google Scholar 

  42. Pinzaru, I.A., Hadaruga, D.I., Hadaruga, N.G., Corpas, L., Grozescu, I., Peter, F.: Hepatoprotective flavonoid bioconjugate/b-cyclodextrin nanoparticles: dSC-molecular modeling correlation. Dig. J. Nanomater. Biostruct. 6, 1605–1617 (2011)

    Google Scholar 

  43. Dimitrić Marković, J.M., Marković, Z.S., Milenković, D., Jeremić, S.: Application of comparative vibrational spectroscopic and mechanistic studies in analysis of fisetin structure. Spectroc. Acta Pt. A-Molec. Biomolec. Spectr. 83, 120–129 (2011)

  44. Miclea, L.M., Vlaia, L., Vlaia, V., Hădărugă, D.I., Mircioiu, C.: Preparation and characterization of inclusion complexes of meloxicam and α-cyclodextrin and β-cyclodextrin. Farmacia 58, 583–593 (2010)

    CAS  Google Scholar 

  45. Friesner, R.A., Banks, J.L., Murphy, R.B., Halgren, T.A., Klicic, J.J., Mainz, D.T., Repasky, M.P., Knoll, E.H., Shelley, M., Perry, J.K., Shaw, D.E., Francis, P., Shenkin, P.S.: Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47, 1739–1749 (2004)

    Article  CAS  Google Scholar 

  46. Szliszka, E., Czuba, Z.P., Domino, M., Mazur, B., Zydowicz, G., Krol, W.: Ethanolic extract of propolis (EEP) enhances the apoptosis-inducing potential of TRAIL in cancer cells. Molecules 14, 738–754 (2009)

    Article  CAS  Google Scholar 

  47. Ogoshi, T., Harada, A.: Chemical sensors based on cyclodextrin derivatives. Sensors 8, 4961–4982 (2008)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Priority Research Centers Program through National Research Foundation of Korea Grant funded by the Korean Government (Ministry of Education, Science and Technology (NRF-2012-0006686) and was partly supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2011-0024008 and NRF-2011-619-E0002). SDG.

Author information

Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul, 143-701, South Korea

    Hwanhee Kim, Jae Min Choi, Muhammad Nazir Tahir, Eunae Cho & Seunho Jung

  2. BioChip Research Center, Hoseo University, Asan, 336-795, South Korea

    Youngjin Choi

  3. Department of Microbial Engineering, College of Engineering, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, 143-701, South Korea

    Yung-Hun Yang

Authors
  1. Hwanhee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae Min Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Youngjin Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Nazir Tahir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yung-Hun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eunae Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seunho Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seunho Jung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H., Choi, J.M., Choi, Y. et al. Enhanced solubility of galangin based on the complexation with methylated microbial cyclosophoraoses. J Incl Phenom Macrocycl Chem 79, 291–300 (2014). https://doi.org/10.1007/s10847-013-0351-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-013-0351-9

Keywords

Search

Navigation