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

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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.

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References

  1. Marchese A, Orhan IE, Daglia M et al (2016) Antibacterial and antifungal activities of thymol: a brief review of the literature. Food Chem 210:402–414

    Article  CAS  Google Scholar 

  2. Jukić M, Miloš M (2005) Catalytic oxidation and antioxidant properties of thyme essential oils (Thymus vulgarae L.) Croat Chem Acta 78:105–110

    Google Scholar 

  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 111:378–382

    Article  Google Scholar 

  4. Del Nobile MA, Conte A, Incoronato AL, Panza O (2008) Antimicrobial efficacy and release kinetics of thymol from zein films. J Food Eng 89:57–63

    Article  Google Scholar 

  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 6:58

    Article  Google Scholar 

  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 22:537–542

    Google Scholar 

  7. Bakkali F, Averbeck S, Averbeck D, Idaomar M (2008) Biological effects of essential oils—a review. Food Chem Toxicol 46:446–475

    Article  CAS  Google Scholar 

  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 15:169–172

    Article  CAS  Google Scholar 

  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 51:63–67

    Article  Google Scholar 

  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 101:809–811

    Article  Google Scholar 

  11. Shapiro S, Meier A, Guggenheim B (1994) The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol 9:202–208

    Article  CAS  Google Scholar 

  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 84:368–376

    Article  CAS  Google Scholar 

  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 37:813–823

    Article  CAS  Google Scholar 

  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. 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 47:2037–2043

    Article  Google Scholar 

  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 581:43–53

    Article  CAS  Google Scholar 

  17. Buyukleyla M, Rencuzogullari E (2009) The effects of thymol on sister chromatid exchange, chromosome aberration and micronucleus in human lymphocytes. Ecotoxicol Environ Saf 72:943–947

    Article  CAS  Google Scholar 

  18. Messner M, Kurkov SV, Jansook P, Loftsson T (2010) Self-assembled cyclodextrin aggregates and nanoparticles. Int J Pharm 387:199–208

    Article  CAS  Google Scholar 

  19. Brewster ME, Loftsson T (2007) Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 59:645–666

    Article  CAS  Google Scholar 

  20. Marques HMC (2010) A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour Fragr J 25:313–326

    Article  Google Scholar 

  21. Sanguansri P, Augustin MA (2006) Nanoscale materials development—a food industry perspective. Trends Food Sci Technol 17:547–556

    Article  CAS  Google Scholar 

  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 128:81–88

    Article  CAS  Google Scholar 

  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 59:247–255

    Article  Google Scholar 

  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 36:872–880

    Article  CAS  Google Scholar 

  25. Moore KE, Flavel BS, Ellis AV, Shapter JG (2011) Comparison of double-to single-walled carbon nanotube electrodes by electrochemistry. Carbon N Y 49:2639–2647

    Article  CAS  Google Scholar 

  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 5:344–363

    Article  CAS  Google Scholar 

  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 90:2137–2140

    Article  CAS  Google Scholar 

  28. Bustamante C, Vesenka J, Tang CL et al (1992) Circular DNA molecules imaged in air by scanning force microscopy. Biochemistry 31:22–26

    Article  CAS  Google Scholar 

  29. Allen MJ, Dong XF, O’Neill TE et al (1993) Atomic force microscope measurements of nucleosome cores assembled along defined DNA sequences. Biochemistry 32:8390–8396

    Article  CAS  Google Scholar 

  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 765:168–178

    Article  Google Scholar 

  31. Bollo S, Ferreyra NF, Rivas GA (2007) Electrooxidation of DNA at glassy carbon electrodes modified with multiwall carbon nanotubes dispersed in chitosan. Electroanalysis 19:833–840

    Article  CAS  Google Scholar 

  32. Sadik OA, Aluoch AO, Zhou A (2009) Status of biomolecular recognition using electrochemical techniques. Biosens Bioelectron 24:2749–2765

    Article  CAS  Google Scholar 

  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 146:42–53

    Article  CAS  Google Scholar 

  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 25:486–493

    Article  CAS  Google Scholar 

  35. Pang D, Thierry AR, Dritschilo A (2015) DNA studies using atomic force microscopy: capabilities for measurement of short DNA fragments. Front Mol Biosci 2:1–7

    Article  CAS  Google Scholar 

  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 5:951–957

    Article  CAS  Google Scholar 

  37. Nafisi S, Hajiakhoondi A, Yektadoost A (2004) Thymol and carvacrol binding to DNA: model for drug-DNA interaction. Biopolymers 74:345–351

    Article  CAS  Google Scholar 

  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 13:4187–4189

    Article  CAS  Google Scholar 

  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 53:1945–1953

    Article  CAS  Google Scholar 

  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 76:419

    Article  Google Scholar 

  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 102:393–399

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

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Authors and Affiliations

  1. Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, AL, 57072-900, Brazil

    Katherine Lozano, Fabricia da Rocha Ferreira, Emanuella G. da Silva, Renata Costa dos Santos, Marilia O. F. Goulart & Fabiane Caxico de Abreu

  2. Grupo de Óptica e Nanoscopia (GON), Instituto de Física, Universidade Federal de Alagoas, Maceió, AL, 57072-900, Brazil

    Samuel T. Souza & Eduardo J. S. Fonseca

  3. Centro de Investigación de los Procesos Redox (CiPRex), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380492, Santiago, Chile

    Claudia Yañez

  4. Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Ignacio Valdivieso 2409, P.O. Box 8940577, Santiago, San Joaquín, Chile

    Paulina Sierra-Rosales

Authors
  1. Katherine Lozano
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  2. Fabricia da Rocha Ferreira
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  3. Emanuella G. da Silva
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  6. Samuel T. Souza
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Correspondence to Fabiane Caxico de Abreu.

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Lozano, K., da Rocha Ferreira, F., da Silva, E.G. et al. Electrochemical and associated techniques for the study of the inclusion complexes of thymol and β-cyclodextrin and its interaction with DNA. J Solid State Electrochem 22, 1483–1493 (2018). https://doi.org/10.1007/s10008-017-3805-y

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  • DOI: https://doi.org/10.1007/s10008-017-3805-y

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