Advertisement

Journal of Solid State Electrochemistry

, Volume 22, Issue 5, pp 1483–1493 | Cite as

Electrochemical and associated techniques for the study of the inclusion complexes of thymol and β-cyclodextrin and its interaction with DNA

  • Katherine Lozano
  • Fabricia da Rocha Ferreira
  • Emanuella G. da Silva
  • Renata Costa dos Santos
  • Marilia O. F. Goulart
  • Samuel T. Souza
  • Eduardo J. S. Fonseca
  • Claudia Yañez
  • Paulina Sierra-Rosales
  • Fabiane Caxico de Abreu
Original Paper
  • 279 Downloads

Abstract

Thymol, a potent agent for microbial, fungal, and bacterial disease, has low aqueous solubility and it is genotoxic, i.e., is capable of damaging deoxyribonucleic acid (DNA). This possible problem of DNA toxicity needs to be solved to allow the use of different doses of thymol. This study characterized the inclusion compound containing thymol and β-cyclodextrin (β-CD) by measuring the interaction between these two components and the ability of thymol to bind DNA in its free and β-CD complexed form. The encapsulation approach using β-CD is particularly useful when controlled target release is desired, and a compound is insoluble, unstable, or genotoxic. The interaction between thymol and DNA has been studied using electrochemical quartz crystal microbalance (EQCM), atomic force microscopy (AFM), and differential pulse voltammetry (DPV). The characterization of the inclusion complex of thymol and β-CD was analyzed by UV-vis spectrophotometry, cyclic voltammetry, and scanning electrochemical microscopy (SECM). Based on the free β-CD by spectrophotometry method, the association constant of thymol with the β-CD was estimated to be 2.8 × 104 L mol−1. The AFM images revealed that in the presence of small concentrations of thymol, the dsDNA molecules appeared less knotted and bent on the mica surface, showing significant damage to DNA. The SECM and voltammetry results both demonstrated that the interaction of thymol-β-CD complex was smaller than the free compound showing that the encapsulation process may be an advantage leading to a reduction of toxic effects and increase of the bioavailability of the drug.

Keywords

Thymol β-Cyclodextrin AFM SECM EQCM DPV 

Notes

Acknowledgements

The authors are grateful to Brazilian agencies CNPq, CAPES, FAPEAL, and Organization of American States (OAS) for financial support.

References

  1. 1.
    Marchese A, Orhan IE, Daglia M et al (2016) Antibacterial and antifungal activities of thymol: a brief review of the literature. Food Chem 210:402–414CrossRefGoogle Scholar
  2. 2.
    Jukić M, Miloš M (2005) Catalytic oxidation and antioxidant properties of thyme essential oils (Thymus vulgarae L.) Croat Chem Acta 78:105–110Google Scholar
  3. 3.
    Monteiro MVB, de Melo Leite AKR, Bertini LM et al (2007) Topical anti-inflammatory, gastroprotective and antioxidant effects of the essential oil of Lippia sidoides Cham. leaves. J Ethnopharmacol 111:378–382CrossRefGoogle Scholar
  4. 4.
    Del Nobile MA, Conte A, Incoronato AL, Panza O (2008) Antimicrobial efficacy and release kinetics of thymol from zein films. J Food Eng 89:57–63CrossRefGoogle Scholar
  5. 5.
    Du E, Gan L, Li Z et al (2015) In vitro antibacterial activity of thymol and carvacrol and their effects on broiler chickens challenged with Clostridium perfringens. J Anim Sci Biotechnol 6:58CrossRefGoogle Scholar
  6. 6.
    Özgüven M, Tansi S (1998) Drug yield and essential oil of Thymus vulgaris L. as in influenced by ecological and ontogenetical variation. Turkish J Agric For 22:537–542Google Scholar
  7. 7.
    Bakkali F, Averbeck S, Averbeck D, Idaomar M (2008) Biological effects of essential oils—a review. Food Chem Toxicol 46:446–475CrossRefGoogle Scholar
  8. 8.
    Baydar H, Saǧdiç O, Özkan G, Karadoǧan T (2004) Antibacterial activity and composition of essential oils from Origanum, Thymbra and Satureja species with commercial importance in Turkey. Food Control 15:169–172CrossRefGoogle Scholar
  9. 9.
    Vardar-Ünlü G, Candan F, Sókmen A et al (2003) Antimicrobial and antioxidant activity of the essential oil and methanol extracts of Thymus pectinatus Fisch. et Mey. Var. pectinatus (Lamiaceae). J Agric Food Chem 51:63–67CrossRefGoogle Scholar
  10. 10.
    Da Silveira Novelino AM, Daemon E, Soares GLG (2007) Evaluation of the acaricide effect of thymol, menthol, salicylic acid, and methyl salicylate on Boophilus Microplus (Canestrini 1887) (Acari: Ixodidae) larvae. Parasitol Res 101:809–811CrossRefGoogle Scholar
  11. 11.
    Shapiro S, Meier A, Guggenheim B (1994) The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol 9:202–208CrossRefGoogle Scholar
  12. 12.
    Manou I, Bouillard L, Devleeschouwer MJ, Barel AO (1998) Evaluation of the preservative properties of Thymus vulgaris essential oil in topically applied formulations under a challenge test. J Appl Microbiol 84:368–376CrossRefGoogle Scholar
  13. 13.
    Stammati A, Bonsi P, Zucco F et al (1999) Toxicity of selected plant volatiles in microbial and mammalian short-term assays. Food Chem Toxicol 37:813–823CrossRefGoogle Scholar
  14. 14.
    Azirak S, Rencuzogullari E (2008) The in vivo genotoxic effects of carvacrol and thymol in rat bone marrow cells. Environ Toxicol.  https://doi.org/10.1002/tox.20380
  15. 15.
    Ündeger Ü, Basaran A, Degen GH, Basaran N (2009) Antioxidant activities of major thyme ingredients and lack of (oxidative) DNA damage in V79 Chinese hamster lung fibroblast cells at low levels of carvacrol and thymol. Food Chem Toxicol 47:2037–2043CrossRefGoogle Scholar
  16. 16.
    Aydin S, Başaran AA, Başaran N (2005) The effects of thyme volatiles on the induction of DNA damage by the heterocyclic amine IQ and mitomycin C. Mutat Res Genet Toxicol Environ Mutagen 581:43–53CrossRefGoogle Scholar
  17. 17.
    Buyukleyla M, Rencuzogullari E (2009) The effects of thymol on sister chromatid exchange, chromosome aberration and micronucleus in human lymphocytes. Ecotoxicol Environ Saf 72:943–947CrossRefGoogle Scholar
  18. 18.
    Messner M, Kurkov SV, Jansook P, Loftsson T (2010) Self-assembled cyclodextrin aggregates and nanoparticles. Int J Pharm 387:199–208CrossRefGoogle Scholar
  19. 19.
    Brewster ME, Loftsson T (2007) Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 59:645–666CrossRefGoogle Scholar
  20. 20.
    Marques HMC (2010) A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour Fragr J 25:313–326CrossRefGoogle Scholar
  21. 21.
    Sanguansri P, Augustin MA (2006) Nanoscale materials development—a food industry perspective. Trends Food Sci Technol 17:547–556CrossRefGoogle Scholar
  22. 22.
    Mulinacci N, Melani F, Vincieri FF et al (1996) 1H-NMR NOE and molecular modelling to characterize thymol and carvacrol b-cyclodextrin complexes. Int J Pharm 128:81–88CrossRefGoogle Scholar
  23. 23.
    Tao F, Hill LE, Peng Y, Gomes CL (2014) Synthesis and characterization of β-cyclodextrin inclusion complexes of thymol and thyme oil for antimicrobial delivery applications. LWT - Food Sci Technol 59:247–255CrossRefGoogle Scholar
  24. 24.
    Polyakov NE, Leshina TV, Konovalova TA et al (2004) Inclusion complexes of carotenoids with cyclodextrins: 1H NMR, EPR, and optical studies. Free Radic Biol Med 36:872–880CrossRefGoogle Scholar
  25. 25.
    Moore KE, Flavel BS, Ellis AV, Shapter JG (2011) Comparison of double-to single-walled carbon nanotube electrodes by electrochemistry. Carbon N Y 49:2639–2647CrossRefGoogle Scholar
  26. 26.
    Loaiza ÓA, Campuzano S, López-Berlanga M et al (2005) Development of a DNA sensor based on alkanethiol self- assembled monolayer-modified electrodes. Sensors 5:344–363CrossRefGoogle Scholar
  27. 27.
    Lyubchenko Y, Shlyakhtenko L, Harrington R et al (1993) Atomic force microscopy of long DNA: imaging in air and under water. Proc Natl Acad Sci U S A 90:2137–2140CrossRefGoogle Scholar
  28. 28.
    Bustamante C, Vesenka J, Tang CL et al (1992) Circular DNA molecules imaged in air by scanning force microscopy. Biochemistry 31:22–26CrossRefGoogle Scholar
  29. 29.
    Allen MJ, Dong XF, O’Neill TE et al (1993) Atomic force microscope measurements of nucleosome cores assembled along defined DNA sequences. Biochemistry 32:8390–8396CrossRefGoogle Scholar
  30. 30.
    de Vasconcellos MCMC, De Oliveira Costa C, da Silva Terto EGEG et al (2016) Electrochemical, spectroscopic and pharmacological approaches toward the understanding of biflorin DNA damage effects. J Electroanal Chem 765:168–178CrossRefGoogle Scholar
  31. 31.
    Bollo S, Ferreyra NF, Rivas GA (2007) Electrooxidation of DNA at glassy carbon electrodes modified with multiwall carbon nanotubes dispersed in chitosan. Electroanalysis 19:833–840CrossRefGoogle Scholar
  32. 32.
    Sadik OA, Aluoch AO, Zhou A (2009) Status of biomolecular recognition using electrochemical techniques. Biosens Bioelectron 24:2749–2765CrossRefGoogle Scholar
  33. 33.
    Nowicka AM, Kowalczyk A, Stojek Z, Hepel M (2010) Nanogravimetric and voltammetric DNA-hybridization biosensors for studies of DNA damage by common toxicants and pollutants. Biophys Chem 146:42–53CrossRefGoogle Scholar
  34. 34.
    Cerreta A, Vobornik D, Di Santo G et al (2012) FM-AFM constant height imaging and force curves: high resolution study of DNA-tip interactions. J Mol Recognit 25:486–493CrossRefGoogle Scholar
  35. 35.
    Pang D, Thierry AR, Dritschilo A (2015) DNA studies using atomic force microscopy: capabilities for measurement of short DNA fragments. Front Mol Biosci 2:1–7CrossRefGoogle Scholar
  36. 36.
    Sawant PD, Watson GS, Nicolau D et al (2005) Hierarchy of DNA immobilization and hybridization on poly-l-lysine using an atomic force microscopy study. J Nanosci Nanotechnol 5:951–957CrossRefGoogle Scholar
  37. 37.
    Nafisi S, Hajiakhoondi A, Yektadoost A (2004) Thymol and carvacrol binding to DNA: model for drug-DNA interaction. Biopolymers 74:345–351CrossRefGoogle Scholar
  38. 38.
    Maeda Y, Fukuda T, Yamamoto H, Kitano H (1997) Regio- and stereoselective complexation by a self-assembled monolayer of thiolated cyclodextrin on a gold electrode. Langmuir 13:4187–4189CrossRefGoogle Scholar
  39. 39.
    Damos FS, Luz RCS, Kubota LT (2007) Electrochemical properties of self-assembled monolayer based on mono-(6-deoxy-6-mercapto)-b-cyclodextrin toward controlled molecular recognition. Electrochim Acta 53:1945–1953CrossRefGoogle Scholar
  40. 40.
    Hernández-Benito J, González-Mancebo S, Calle E et al (1999) A practical integrated approach to supramolecular chemistry. I. Equilibria in inclusion phenomena. J Chem Educ 76:419CrossRefGoogle Scholar
  41. 41.
    Nieddu M, Rassu G, Boatto G, Bosi P, Trevisi P, Giunchedi P, Carta AGE, Nieddu M, Rassu G et al (2014) Improvement of thymol properties by complexation with cyclodextrins: in vitro and in vivo studies. Carbohydr Polym 102:393–399CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Katherine Lozano
    • 1
  • Fabricia da Rocha Ferreira
    • 1
  • Emanuella G. da Silva
    • 1
  • Renata Costa dos Santos
    • 1
  • Marilia O. F. Goulart
    • 1
  • Samuel T. Souza
    • 2
  • Eduardo J. S. Fonseca
    • 2
  • Claudia Yañez
    • 3
  • Paulina Sierra-Rosales
    • 4
  • Fabiane Caxico de Abreu
    • 1
  1. 1.Instituto de Química e BiotecnologiaUniversidade Federal de AlagoasMaceióBrazil
  2. 2.Grupo de Óptica e Nanoscopia (GON), Instituto de FísicaUniversidade Federal de AlagoasMaceióBrazil
  3. 3.Centro de Investigación de los Procesos Redox (CiPRex), Facultad de Ciencias Químicas y FarmacéuticasUniversidad de ChileSantiagoChile
  4. 4.Programa Institucional de Fomento a la Investigación, Desarrollo e InnovaciónUniversidad Tecnológica MetropolitanaSantiagoChile

Personalised recommendations