Advertisement

Host–guest system of 4-nerolidylcatechol in 2-hydroxypropyl-β-cyclodextrin: preparation, characterization and molecular modeling

  • Líllian Amélia Soares
  • Ana Flávia Vasconcelos Borges Leal
  • Leonardo Fernandes Fraceto
  • Elaine Rose Maia
  • Inês Sabioni Resck
  • Massuo Jorge Kato
  • Eric de Sousa Gil
  • Aparecido Ribeiro de Sousa
  • Luiz Carlos da Cunha
  • Kênnia Rocha Rezende
Original Article

Abstract

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV–Vis, 1H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a BS-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 ± 837 M−1. Stoichiometry was established by the UV spectrophotometer using Job’s plot method and, also confirmed by molecular modeling. Data from 1H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-β-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.

Keywords

4-Nerolidylcatechol 2-Hydroxypropyl-β-cyclodextrin Inclusion complex 1H-NMR and molecular dynamics 

Notes

Acknowledgments

This work was partly supported by a grant from CNPq and SECTEC-GO. The authors acknowledge Dr. Massayoshi Yoshida and Dr. Luiz Carlos Roque for the NMR 500 MHz data acquisition. We are especially grateful to Prof. Harry Pearson for English corrections on the manuscript.

References

  1. 1.
    Ropke, C.D., da Silva, V.V., Kera, C.Z., Miranda, D.V., de Almeida, R.L., Sawada, T.C., Barros, S.B.M.: In vitro and in vivo inhibition of skin matrix metalloproteinases by pothomorphe umbellata root extract. Photochem. Photobiol. 82(2), 439–442 (2006)CrossRefGoogle Scholar
  2. 2.
    Ropke, C.D., Kaneko, T.M., Rodrigues, R.M., Silva, V.V., Barros, S., Sawada, T.C.H., Kato, M.J., Barros, S.B.M.: Evaluation of percutaneous absorption of 4-nerolidylcathecol from four topical formulations. Int. J. Pharm. 249(1–2), 109–116 (2002)CrossRefGoogle Scholar
  3. 3.
    Ropke, C.D., Meirelles, R.R., Silva, V.V., Sawada, T.C.H., Barros, S.B.M.: Pothomorphe umbellata extract prevents α-tocopherol depletion after UV-irradiation. Photochem. Photobiol. 78(5), 436–439 (2003)CrossRefGoogle Scholar
  4. 4.
    Ropke, C.D., Sawada, T.C.H., da Silva, V.V., Michalany, N.S., Barros, S.B.M.: Photoprotective effect of Pothomorphe umbellata root extract against ultraviolet radiation induced chronic skin damage in the hairless mouse. Clin. Exp. Dermatol. 30(3), 272–276 (2005)CrossRefGoogle Scholar
  5. 5.
    Barros, S.B.M., Ropke, C.D.: Use of Pothomorphe umbellata extract, composition on basis of Pothomorphe umbellata extract and method of application on the Pothomorphe umbellata extract. (Fundação de Amparo a Pesquisa do Estado de São Paulo—FAPESP, Brazil; Universidade de São Paulo—USP). PCT Int. Appl. (2004), CODEN: PIXXD2 WO 2004026323 A1Google Scholar
  6. 6.
    Perazzo, F.F., Souza, G.H.B., Lopes, W., Cardoso, L.G.V., Carvalho, J.C.T., Nanayakkara, N.P.D., Bastos, J.K.: Anti-inflammatory and analgesic properties of water–ethanolic extract from Pothomorphe umbellata (Piperaceae) aerial parts. J. Ethnopharmacol. 99(2), 215–220 (2005)CrossRefGoogle Scholar
  7. 7.
    Mongelli, E., Desmarchelier, F., Coussio, J., Ciccia, G.: Antimicrobial activity and interaction with DNA of medicinal plants from the Peruvian Amazon region. Rev. Argent. Microbiol. 27(4), 199–203 (1995)Google Scholar
  8. 8.
    Mongelli, E., Romano, A., Desmarchelier, C., Coussio, J., Ciccia, G.: A cytotoxic catechol derivative from Pothomorphe peltata inhibits topoisomerase I activity. Planta Med. 65(4), 376–378 (1999)CrossRefGoogle Scholar
  9. 9.
    Valadares, M.C., Rezende, K.R., Pereira, E.R., Sousa, M.C., Gonçalves, B., de Assis, J.C., Kato, M.J.: Protective effects of 4-nerolidylcatechol against genotoxicity induced by cyclophosphamide. Food Chem. Toxicol. 45(10), 1975–1978 (2007)CrossRefGoogle Scholar
  10. 10.
    Vandelli, M.A., Salvioli, G., Mucci, A., Panini, R., Malmusi, L.: 2-Hydroxypropyl-β-cyclodextrin complexation with ursodeoxycholic acid. Int. J. Pharm. 118(1), 77–83 (1995)CrossRefGoogle Scholar
  11. 11.
    Fernandes, C.M., Vieira, M.T., Veiga, F.J.B.: Physicochemical characterization and in vitro dissolution behavior of nicardipine–cyclodextrins inclusion compounds. Eur. J. Pharm. Sci. 15(1), 79–88 (2002)CrossRefGoogle Scholar
  12. 12.
    Archontaki, H.A., Vertzoni, M.V., Athanassiou-Malaki, M.H.: Study on the inclusion complexes of bromazepam with β- and β-hydroxypropyl-cyclodextrins. J. Pharm. Biomed. Anal. 28(3–4), 761–769 (2002)CrossRefGoogle Scholar
  13. 13.
    Duchêne, D., Wouessidjewe, D.: Pharmaceutical uses of cyclodextrins and derivatives. Drug Dev. Ind. Pharm. 16(17), 2487–2499 (1990)CrossRefGoogle Scholar
  14. 14.
    Leroy-Lechat, F., Wouessidjewe, D., Andreux, J.P., Puisieux, F., Duchêne, D.: Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives. Int. J. Pharm. 101(1–2), 97–103 (1994)CrossRefGoogle Scholar
  15. 15.
    Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3(12), 1023–1035 (2004)CrossRefGoogle Scholar
  16. 16.
    Hirsch, W., Fried, V., Altman, L.: Effect of cyclodextrins on sparingly soluble salts. J. Pharm. Sci. 74(10), 1123–1125 (1985)CrossRefGoogle Scholar
  17. 17.
    Rezende, K.R., Barros, S.B.M.: Quantification of 4-nerolidylchatecol of Pothomorphe umbellata (Piperaceae) in rat plasma samples by HPLC UV. Braz. J. Pharm. Sci. 40(3), 373–380 (2004)Google Scholar
  18. 18.
    Gustafson, K.R., Cardellina, J.H., McMahon, J.B., Pannell, L.K., Cragg, G.M., Boyd, M.R.: The peltatolls, nove HIV-inhibitory catechol derivates from P. peltata. J. Org. Chem. 57(10), 2809–2811 (1992)CrossRefGoogle Scholar
  19. 19.
    Higuchi, T., Connors, K.A.: Phase solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)Google Scholar
  20. 20.
    Job, P.: Formation and stability of inorganic complexes in solution. Ann. Chim. 9, 113–203 (1928)Google Scholar
  21. 21.
    Calabro, M.L., Tommasini, S., Donato, P., Ranieri, D., Stancanelli, R., Ficarra, P., Ficarra, R., Costa, C., Catania, S., Rustichelli, C., Gamberini, G.: Effects of α- and β-cyclodextrin complexation on the physico-chemical properties and antioxidant activity of some 3-hydroxyflavones. J. Pharm. Biomed. Anal. 35(2), 364–367 (2004)Google Scholar
  22. 22.
    Materials Studio Software and Insight II Software, Accelrys, 9685 Scranton Road, San Diego, CA 92121-3752, USAGoogle Scholar
  23. 23.
    Hwang, M.J., Stockfisch, T.P., Hagler, A.T.: Derivation of Class II force fields. 2. Derivation and characterization of a Class II force field, CFF93, for the alkyl functional group and alkane molecules. J. Am. Chem. Soc. 116(6), 2515–2525 (1994)CrossRefGoogle Scholar
  24. 24.
    Sun, H., Mumby, S.J., Maple, J.R., Hagler, A.T.: An ab initio CFF93 all-atom force field for polycarbonates. J. Am. Chem. Soc. 116(7), 2978–2987 (1994)CrossRefGoogle Scholar
  25. 25.
    Abola, E.E., Bernstein, F.C., Bryant, S.H., Koetzle, T.F., Weng, J., Allen, F.H., Bergerhoff, G., Sievers, R.: Protein Data Bank. In Allen, F.H., Bergerhoff, G., Sievers, R. (eds.) Crystallographic Databases—Information Content, Software Systems, Scientific Applications. Data Commission of International Union of Crystallography, Cambridge (1987)Google Scholar
  26. 26.
    Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000) http://www.rcsb.org/PDB. Accessed 12 June 2008
  27. 27.
    Sharff, A.J., Rodseth, L.E., Quiocho, F.A.: Refined 1.8-.ANG. structure reveals the mode of binding of beta-cyclodextrin to the maltodextrin binding protein. Biochemistry 32(40), 10553–10559 (1993)CrossRefGoogle Scholar
  28. 28.
    Connolly, M.L.: Solvent-accessible surfaces of proteins and nucleic acids. Science 221(4612), 709–713 (1983)CrossRefGoogle Scholar
  29. 29.
    Connolly, M.L.: Shape distributions of protein topography. Biopolymers 32(9), 1215–1236 (1992)CrossRefGoogle Scholar
  30. 30.
    Loftsson, T., Brewster, E.M.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. Int. J. Pharm. Sci. 85(10), 1017–1025 (1996)CrossRefGoogle Scholar
  31. 31.
    Imonigie, J.A., Macartney, D.H.: Effects of cyclodextrin inclusion on the kinetics on the outer-sphere oxidation of 4-tert-butylcatechol by transition metal complexes in acidic aqueous media. Inorg. Chem. 32(6), 1007–1012 (1993)CrossRefGoogle Scholar
  32. 32.
    Tønnesen, H.H., Ma´sson, M., Loftsson, T.: Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int. J. Pharm. 244(1–2), 127–135 (2002)CrossRefGoogle Scholar
  33. 33.
    Blanco, J., Vila-Jato, J.L., Otero, F., Anguiano, S.: Influence of method of preparation on inclusion complexes of naproxen with different cyclodextrins. Drug. Dev. Ind. Pharm. 17(7), 943–945 (1991)CrossRefGoogle Scholar
  34. 34.
    Pitha, J., Milecki, J., Fales, H., Pannell, L., Uekama, K.: Hydroxypropyl-β-cyclodextrin: preparation and characterization; effects on solubility of drugs. Int. J. Pharm. 29(1), 73–82 (1986)CrossRefGoogle Scholar
  35. 35.
    Ventura, C.A., Tirendi, S., Puglisi, G., Bousquet, E., Panza, L.: Solid-state properties of powders in the formulation and processing of solid dosage forms. Int. J. Pharm. 14(1), 1–13 (1997)CrossRefGoogle Scholar
  36. 36.
    Sacoman, J.L., Monteiro, K.M., Possenti, A., Figueira, G.M., Foglio, M.A., Carvalho, J.E.: Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata. Braz. J. Med. Biol. Res. 41(5), 411–415 (2008)CrossRefGoogle Scholar
  37. 37.
    Gibaud, S., Zirar, S.B., Mutzenhardt, P., Fries, I., Astier, A.: Melarsoprol–cyclodextrins inclusion complexes. Int. J. Pharm. 306(1–2), 107–121 (2005)CrossRefGoogle Scholar
  38. 38.
    Xinyi, T., Lindenbaum, S.: Studies on complexation between β-cyclodextrin and bile salts. Int. J. Pharm. 74(1–2), 127–135 (1991)Google Scholar
  39. 39.
    Veiga, F.J.B., Fernandes, C.M., Carvalho, R.A., Geraldes, C.F.G.C.: Molecular modeling and 1H-NMR: ultimate tools for the investigation of tolbutamide: β-cyclodextrin and tolbutamide: hydropropyl-β-cyclodextrin complexes. Chem. Pharm. Bull. 49(10), 1251–1256 (2001)CrossRefGoogle Scholar
  40. 40.
    Martin Del Valle, E.M.: Cyclodextrins and their uses: a review. Process Biochem. 39(9), 1033–1046 (2004)CrossRefGoogle Scholar
  41. 41.
    Araujo, M.V.G., Vieira, E.K.B., Lázaro, G.S., Conegero, L.S., Ferreira, O.P., Almeida, L.E., Barreto, L.S., Costa Junior, N.B.C., Gimenez, I.F.: Inclusion complexes of pyrimethamine in 2-hydroxypropyl-β-cyclodextrin: characterization, phase solubility and molecular modelling. Bioorg. Med. Chem. 15(17), 5752–5759 (2007)CrossRefGoogle Scholar
  42. 42.
    Soares, L.A.: Preparação e caracterização do complexo de inclusão do 4-nerolidilcatecol em hidroxipropil-β-ciclodextrina. M.Sc. Thesis, Universidade Federal de Goiás, Goiânia, GO (2007)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Líllian Amélia Soares
    • 1
  • Ana Flávia Vasconcelos Borges Leal
    • 1
  • Leonardo Fernandes Fraceto
    • 2
  • Elaine Rose Maia
    • 3
  • Inês Sabioni Resck
    • 3
  • Massuo Jorge Kato
    • 4
  • Eric de Sousa Gil
    • 1
  • Aparecido Ribeiro de Sousa
    • 5
  • Luiz Carlos da Cunha
    • 1
  • Kênnia Rocha Rezende
    • 1
  1. 1.Laboratório de Biofarmácia e Farmacocinética, Faculdade de FarmáciaUniversidade Federal de Goiás, Praça UniversitáriaGoiâniaBrazil
  2. 2.Departamento de Engenharia AmbientalUniversidade Estadual PaulistaSorocabaBrazil
  3. 3.Instituto de QuímicaUniversidade de BrasíliaBrasíliaBrazil
  4. 4.Departamento de Química Fundamental, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  5. 5.Instituto de QuimicaUniversidade Federal de GoiásGoiâniaBrazil

Personalised recommendations