Skip to main content

Advertisement

SpringerLink
Log in

Immunomodulatory effects of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone from Petasites hybridus and its synthesized benzoxazepine derivatives

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

1-(6-Hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone (1), isolated from the roots of Petasites hybridus L., and a series of synthetic benzoxazepine derivatives of compound 1 (2–6) were evaluated for their immunomodulatory effects. The compounds were evaluated for their effects on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using luminol- and lucigenin-based chemiluminescence (CL) assays, and their effect on chemotactic migration of PMNs was assessed using the Boyden chamber technique. Compound 1 exhibited stronger inhibition than acetylsalicylic acid (ASA) on luminol-enhanced CL of PMNs. It also inhibited PMN chemotaxis with an IC50 value comparable to that of ibuprofen. Of the compounds tested, 5 was the most effective in inhibiting luminol-enhanced CL and also strongly inhibited lucigenin-enhanced CL with IC50 values lower than that of ASA. Compound 2 was the most active in inhibiting migration of PMNs and was five times stronger than ibuprofen. The results suggest that compound 1 and its synthesized benzoxazepine derivatives, especially compounds 2 and 5, were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as leads for the development of new immunomodulatory agents.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Beutler B (2004) Innate immunity: an overview. Mol Immunol 40:845–859

    Article  CAS  PubMed  Google Scholar 

  2. Afonso V, Champy R, Mitrovic D, Collin P, Lomri A (2007) Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 74:324–329

    Article  CAS  PubMed  Google Scholar 

  3. Cottineau B, Toto P, Marot C, Pipaud A, Chenault J (2002) Synthesis and hypoglycemic evaluation of substituted pyrazole-4-carboxylic acids. Bioorg Med Chem Lett 12:2105–2108

    Article  CAS  PubMed  Google Scholar 

  4. Kalkhambkar RG, Aridoss G, Kulkarni GM (2011) Synthesis and biological activities of novel ethers of quinolinone linked with coumarins. Monatshefte fur Chemie 142:305–315

    Article  CAS  Google Scholar 

  5. Ghate M, Manohar D, Kulkarni VR, Shobha SY (2003) Kattimani synthesis of vanillin ethers from 4-(bromomethyl) coumarins as anti-inflammatory agents. Eur J Med Chem 38:297–302

    Article  CAS  PubMed  Google Scholar 

  6. Khan IA, Kulkarni MV, Sun CM (2005) One pot synthesis of oxygenated tri-heterocycles as anti-microbial agents. Eur J Med Chem 40:1168–1172

    Article  CAS  PubMed  Google Scholar 

  7. Rostom SAF, Shalaby MA, El-Demellawy MA (2003) Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A novel class of potential antitumor and anti-HCV agents. Eur J Med Chem 38:959–974

    Article  CAS  PubMed  Google Scholar 

  8. Manna K, Agrawal YK (2009) Microwave assisted synthesis of new indophenazine 1,3,5-trisubstituted pyrazoline derivatives of benzofuran and their antimicrobial activity. Bioorg Med Chem Lett 19:2688–2692

    Article  CAS  PubMed  Google Scholar 

  9. Khaleghi F, Din LB, Charati FR, Yaacob WA, Khalilzadeh MA (2011) A new bioactive compound from the roots of Petasites hybridus. Phytochem Lett 4:254–258

    Article  CAS  Google Scholar 

  10. Eaton J (1998) Butterbur, herbal help for migraine. Nat Pharm 2:23–24

    Google Scholar 

  11. Mauskop A (2000) Petasites hybridus: ancient medicinal plant is effective prophylactic treatment for migraine. Townsend Lett 202:104–106

    Google Scholar 

  12. Scheidegger C, Dahinden C, Wiesmann U (1998) Effects of extracts and of individual components from Petasites on prostaglandin synthesis in cultured skin fibroblasts and on leucotriene synthesis in isolated human peripheral leucocytes. Pharm Acta Helvetiae 72:376–378

    CAS  Google Scholar 

  13. Thomet OAR, Schapowal A, Heinisch IVWM, Wiesmann UN, Simon HU (2002) Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis. Int Immunopharmacol 2:997–1006

    Article  CAS  PubMed  Google Scholar 

  14. Berger D, Burkard W, Schaffner W (1998) Influence of Petasites hybridus on dopamine-D2 and histamine-H1 receptors. Pharm Acta Helv 72:373–375

    CAS  PubMed  Google Scholar 

  15. Danesch UC (2004) Petasites hybridus (Butterbur root) extract in the treatment of asthma—an open trial. Altern Med Rev 9:54–62

    PubMed  Google Scholar 

  16. Coyne WE, Cusic JW (1967) Antiinflammatory dialkylaminoalkylureas. J Med Chem 10:541–546

    Article  CAS  PubMed  Google Scholar 

  17. Jilek JO, Pomykacek J, Metysova J (1965) Neurotropic and psychotropic substances. III. Derivatives of dibenz[b,f][1,4]oxazepine. Collect Czechoslov Chem Commun 30:463–471

    Article  CAS  Google Scholar 

  18. Schmutz J, Hunziker F, Stille G (1967) Chemical structure and pharmacological activity of a new group of tricyclic neuroleptics. XI. Heterocycles with seven atoms. Eur J Med Chem (Chim Ther) 2:424–429

    CAS  Google Scholar 

  19. Coyne WE, Cusic JW (1968) Anticonvulsant semicarbazides. J Med Chem 11:1158–1160

    Article  CAS  PubMed  Google Scholar 

  20. Fiorentino A, D’Abrosca B, Pacifico S, Cefarelli G, Uzzo P, Monaco P (2007) Natural dibenzoxazepinones from leaves of Carex distachya: structural elucidation and radical scavenging activity. Bioorg Med Chem Lett 17:636–639

    Article  CAS  PubMed  Google Scholar 

  21. Kamei K, Maeda N, Nomura K, Shibata M, Katsuragi-Ogino R, Koyama M, Nakajima M, Inoue T, Ohno T, Tatsuoka T (2006) Synthesis, SAR studies, and evaluation of 1,4-benz oxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: discovery of piclozotan. Bioorg Med Chem 14:1978–1992

    Article  CAS  PubMed  Google Scholar 

  22. Lowe EW Jr, Ferrebee A, Rodriguez AL, Conn J, Meiler J (2010) 3D-QSAR CoMFA study of benzoxazepine derivatives as mGluR5 positive allosteric modulators. Bioorg Med Chem Lett 20:5922–5924

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Uto Y, Ueno Y, Kiyotsuka Y, Miyazawa Y, Kurata H, Ogata T, Takagi T, Wakimoto S, Ohsumi J (2011) Discovery of novel SCD1 inhibitors: 5-alkyl-4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,41-piperidine] analogs. Eur Med Chem 46:1892–1896

    Article  CAS  Google Scholar 

  24. Khaleghi F, Din LB, Jantan I, Yaakob WA, Khalilzadeh A (2011) A facile synthesis of novel 1,4-benzoxazepine-2-one derivatives. Tetrahedron Lett 52:7182–7184

    Article  CAS  Google Scholar 

  25. Jantan I, Harun NH, Septama AW, Murad S, Mesaik MA (2011) Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants. J Nat Med 65:400–405

    Article  PubMed  Google Scholar 

  26. Sacerdote P, Massi P, Panerai AE (2000) In vivo and in vitro treatment with the synthetic cannabinoid CP55,940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors. J Neuroimmunol 109:155–163

    Article  CAS  PubMed  Google Scholar 

  27. Arnhold J (2004) Properties, functions, and secretion of human myeloperoxidase. Biochemistry 69:4–9

    CAS  PubMed  Google Scholar 

  28. Rathakrishnan C, Tiku ML (1993) Lucigenin-dependent chemiluminescence in articular chondrocytes. Free Radic Biol Med 15:143–149

    Article  CAS  PubMed  Google Scholar 

  29. Parij NAM, Nagy AM, Fondu P, Neve J, Parolaro D (1998) Effects on nonsteroidal anti-inflammatory drugs on the luminol- and lucigenin-amplified chemiluminescence of human neutrophils. Eur Pharmacol 352:299–305

    Article  CAS  Google Scholar 

  30. Allen A (1986) Phagocytic leucocytic oxygen activities and chemiluminescence: a kinetic approach to analysis. In: Deluca M et al (eds) Methods in enzymology. bioluminescence and chemiluminescence, vol 133B. Academic Press, New York, pp 449–493

    Chapter  Google Scholar 

  31. Spisani S, Vanzini G, Traniello S (1979) Inhibition of human leucocytes locomotion by anti-inflammatory drugs. Experientia 35:803–804

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Higher Education, Malaysia, under the Fundamental Research Grant Scheme (FRGS)(grant number 03-FRGS0029-2010).

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Fatemeh Khaleghi

  2. Faculty of Pharmacy, Drug and Herbal Research Center, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Ibrahim Jantan & Syed Nasir Abbas Bukhari

  3. Faculty of Science and Technology, School of Chemical Sciences and Food Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia

    Laily Bin Din & Wan A. Yaacob

  4. Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Mazandaran, Iran

    Mohammad A. Khalilzadeh

Authors
  1. Fatemeh Khaleghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ibrahim Jantan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laily Bin Din
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wan A. Yaacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad A. Khalilzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Syed Nasir Abbas Bukhari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ibrahim Jantan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khaleghi, F., Jantan, I., Din, L.B. et al. Immunomodulatory effects of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone from Petasites hybridus and its synthesized benzoxazepine derivatives. J Nat Med 68, 351–357 (2014). https://doi.org/10.1007/s11418-013-0805-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-013-0805-9

Keywords

Search

Navigation