Synthesis of hydroxycoumarins and hydroxybenzo[f]- or [h]coumarins as lipid peroxidation inhibitors

https://doi.org/10.1016/j.bmcl.2008.12.098Get rights and content

Abstract

Substituted hydroxycoumarins and 7- or 8-hydroxybenzo[f]coumarins were prepared by the treatment of phenols and naphthalenediols, respectively, with malic acid and H2SO4 under microwave irradiation. 7- or 8-Hydroxybenzo[f]coumarins and 6-hydroxybenzo[h]coumarin were synthesized by the reaction of naphthalenediols with ethylpropiolate in the presence of ZnCl2 in refluxing dioxane. The compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase and (v) to inhibit in vivo the carrageenin-induced rat paw edema. Most of them are potent superoxide anion scavengers and inhibit in vitro lipid peroxidation. The majority of the compounds did not show high lipoxygenase inhibitory activity. No differences were observed between biological responses of hydroxycoumarins and hydroxybenzocoumarins. Compound 3i was found to present a promising antioxidant profile.

Section snippets

Acknowledgments

The authors gratefully acknowledge support for part of this work through the program PYTHAGORAS II of EPEAEK II (MIS: 97436/073). We would like to thank Dr. C. Hansch and Biobyte Corp. 201 West 4th Street, Suite 204, Claremont, CA 91711, USA for free access to the C-QSAR program.

References and notes (36)

  • M.C. Laufer et al.

    J. Catal.

    (2003)
  • M. Curini et al.

    Bioorg. Med. Chem. Lett.

    (2004)
  • E. Galariniotou et al.

    Tetrahedron

    (2007)
  • V. Baldoumi et al.

    Tetrahedron

    (2006)
  • D.N. Nicolaides et al.

    Eur. J. Med. Chem.

    (2004)
  • R. O’Kennedy et al.

    Coumarins: Biology, Applications and Mode of Action

    (1997)
  • D.H. Murray et al.
    (1982)
  • K.C. Fylaktakidou et al.

    Curr. Pharm. Des.

    (2004)
  • F. Borges et al.

    Curr. Med. Chem.

    (2005)
  • A. Lacy et al.

    Curr. Pharm. Des.

    (2004)
  • I. Kostova

    Curr. Med. Chem. Anticancer Agents

    (2005)
  • C. Kontogiorgis et al.

    J. Med. Chem.

    (2005)
  • B. Ramesh et al.

    J. Med. Food

    (2006)
  • A. Chilin et al.

    J. Med. Chem.

    (2008)
  • S. Sethna et al.

    Org. React.

    (1953)
  • B.M. Trost et al.

    J. Am. Chem. Soc.

    (2003)
  • H. Wulff et al.

    J. Med. Chem.

    (1998)
  • T.-S. Li et al.

    J. Chem. Res., Synop.

    (1998)
  • Cited by (195)

    View all citing articles on Scopus
    View full text