Skip to main content
SpringerLink
Log in

Substituted 9-benzyladenines: Inhibitors of inflammation associated with the delayed hypersensitivity skin reaction

  • Immunosuppression and Inflammation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Members of a group of substituted 9-benzyladenines have been identified as effective inhibitors of inflammatory aspects of the delayed hypersensitivity skin reaction in the guinea-pig. Inhibitory activity was demonstrable in the efferent arc of the cell-mediated tuberculin and contact dermatitis (2,4-dinitrochlorobenzene) reactions. One of the compounds, 2-amino-9-benzyladenine, inhibited both turpentine-induced and histamine-induced inflammation in the skin. The toxicity and inhibitory activities of some of these compounds are discussed, and reference is made to the structurally related mercaptopurines.

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

Similar content being viewed by others

References

  1. H.S. Lawrence,Similarities between Homograft Rejection and Tuberculin-Type Allergy: A Review of Recent Experimental Findings, Ann. N.Y. Acad. Sci.64, 826 (1957).

    PubMed  Google Scholar 

  2. B.H. Waksman,Auto-Immunization and the Lesions of Auto-Immunity, Medicine41, 93 (1962).

    PubMed  Google Scholar 

  3. J.W. Uhr,Delayed Hypersensitivity, Physiol. Rev.46, 359 (1966).

    PubMed  Google Scholar 

  4. B. Benacerraf andE. Green,Cellular Hypersensitivity, A. Rev. Med.20, 141 (1969).

    Article  Google Scholar 

  5. P. Stastny andM. Ziff,Macrophage Migration Inhibition and Cytotoxicity in Acute and Chronic Inflammation, Immunopathology of Inflammation, Proc. Symp. 1970 (Excerpta Medica, Amsterdam 1971).

    Google Scholar 

  6. M. Ziff,Pathophysiology of Rheumatoid Arthritis, Fed. Proc.32, 131 (1973).

    PubMed  Google Scholar 

  7. P. Stastny,Lymphokines in the Rheumatoid Joint Arthritis Rheum.16, 572 (1973).

    Google Scholar 

  8. P.A. Bacon, A. Cracchiolo, R. Bluestone andL.S. Goldberg,Cell-Mediated Immunity to Synovial Antigens in Rheumatoid Arthritis, Lancet2, 699 (1973).

    Article  PubMed  Google Scholar 

  9. R.S. Schwartz,Immunosuppressive Drugs, Prog. Allergy9, 246–303 (1965).

    Google Scholar 

  10. T. Makinodan, G.W. Santos andR.P. Quinn,Immunosuppressive Drugs, Pharmac. Rev.22, 189 (1970).

    Google Scholar 

  11. A.D. Steinberg, P.H. Plotz, S.M. Wolff, V.G. Wong, S.G. Agus andJ.L. Decker,Cytotoxic Drugs in Treatment of Nonmalignant Diseases, Ann. Int. Med.76, 619 (1972).

    PubMed  Google Scholar 

  12. A.D. Steinberg,Efficacy of Immunosuppressive Drugs in Rheumatic Diseases, Arthritis Rheum.16, 92 (1973).

    PubMed  Google Scholar 

  13. H.L. Spiegelberg andP.A. Miescher,The Effect of 6-Mercaptopurine and Aminopterin on Experimental Immune Thyroiditis in Guinea-Pigs, J. exp. Med.118, 869 (1963).

    Article  PubMed  Google Scholar 

  14. J.L. Turk,Studies on the Mechanism of Action of Methotrexate and Cyclophosphamide on Contact Sensitivity in the Guinea-Pig, Int. Arch. Allergy Appl. Immun.24, 191 (1964).

    Google Scholar 

  15. R.M. Friedmann,Inhibition of Established Tuberculin Hypersensitivity by Methotrexate, Proc. Soc. exp. Biol. Med.116, 471 (1974).

    Google Scholar 

  16. R.W. Prichard andD.M. Hayes,The Effects of Aminopterin on Guinea-Pig Tuberculosis, Am. J. Path.38, 325 (1961).

    PubMed  Google Scholar 

  17. Y. Borel andR. Schwartz,Inhibition of Immediate and Delayed Hypersensitivity in the Rabbit by 6-Mercaptopurine, J. Immun.92, 754 (1964).

    PubMed  Google Scholar 

  18. Y. Borel, M. Fauconnet andP.A. Miescher,The Effect of 6-Mercaptopurine (6-MP) and Methotrexate (MTX) on Passive Delayed Hypersensitivity Reactions, Int. Arch. Allergy Appl. Immun.33, 583 (1968).

    Google Scholar 

  19. J.R. Hoyer, L.W. Hoyer, R.A. Good andR.M. Condie,The Effect of 6-Mercaptopurine on Delayed Hypersensitivity in Guinea-Pigs, J. exp. Med.116, 679 (1962).

    Article  PubMed  Google Scholar 

  20. S.M. Phillips andB. Zweiman,Mechanisms in the Suppression of Delayed Hypersensitivity in the Guinea-Pig by 6-Mercaptopurine, J. exp. Med.137, 1494 (1973).

    Article  PubMed  Google Scholar 

  21. R. Vinegar, W. Schreiber andR. Hugo,Inhibitory Effects of Immunosuppressive Agents on Adjuvant Arthritis (AA) and Delayed Skin Reactions (DSR), Pharmacologist10, 184, Abs. 170 (1968).

    Google Scholar 

  22. G.B. Elion, S. Callahan, S. Bieber, G.H. Hitchings andR.W. Rundles,A Summary of Investigations with 6-[(1-Methyl-4-Nitro-5-Imidazolyl)Thio]Purine (B.W. 57-322), Cancer Chemother. Rep.14, 93 (1961).

    Google Scholar 

  23. G.H. Hitchings andG.B. Elion,The Role of Antimetabolites in Immunosuppression and Transplantation, Accounts Chem. Res.2, 202 (1969).

    Article  Google Scholar 

  24. H.E. Sarles, F.D. Thomas, A.R. Remmers, Jr., C.O. Canales, G.H. Smith andG.A. Beathard,A Review of the Actions and Effects of Immunosuppressive Drugs, Tex. Rep. Biol. Med.27, 327 (1969).

    PubMed  Google Scholar 

  25. A.H. Chalmers, L.A. Burgoyne andA.W. Murray,Antineoplastic and Immunosuppressive Drugs I: Biochemical and Clinical Pharmacological Considerations, Drugs3, 227 (1972).

    PubMed  Google Scholar 

  26. M.C. Berenbaum,Immunosuppressive Agents, Br. Med. Bull.21, 140 (1965).

    PubMed  Google Scholar 

  27. J.R. Bertino, B.L. Hillcoat andD.G. Johns,Folate Antagonists: Some Biochemical and Pharmacological Considerations, Fed. Proc.26, 893 (1967).

    PubMed  Google Scholar 

  28. G.B. Elion Biochemistry and Pharmacology of Purine Analogues, Fed. Proc.26, 898 (1967).

    PubMed  Google Scholar 

  29. J.L. Turk andD.A. Willoughby,An Analysis of the Multiplicity of the Effects of Antilymphocyte Serum-A Comparison with the Action of Other Immunosuppressive Agents in the Cell-Mediated Immune Response and Non-Specific Inflammation, Antibiot. Chemother.15, 267 (1969).

    PubMed  Google Scholar 

  30. R.J. Wojnar, K.A. Losee andR.J. Brittain,Structure-Activity Profile of Substituted Purines and Inflammation in the Delayed Hypersensitivity Skin Reaction, Agents and Actions5, 145 (1975).

    PubMed  Google Scholar 

  31. S.M. Hess andR.C. Millonig,Assays for Anti-Inflammatory Agents, Inflammation, Mechanisms and Control (Academic Press, New York 1972), p. 1–12.

    Google Scholar 

  32. J.R. David, S. Al-Askari, H.S. Lawrence andL. Thomas,Delayed Hypersensitivity in vitro I The Specificity of Inhibition of Cell Migration by Antigens, J. Immun.93, 264 (1964).

    PubMed  Google Scholar 

  33. G.L. Floersheim,Screening auf Antirheumatica am Modell der Tuberkulinreaktion, Helv. Physiol. Acta22, 92 (1964).

    Google Scholar 

  34. J.A. Montgomery andH.J. Thomas,On the Alkylation of Adenine, J. Heterocycl. Chem.1, 115 (1964).

    Google Scholar 

  35. J.A. Montgomery andK. Hewson,Synthesis of Potential Anticancer Agents. XX. 2-Fluoropurines, J. Am. Chem. Soc.82, 463 (1960).

    Article  Google Scholar 

  36. J. Davoll,A Synthesis of Crotonoside., J. Am. Chem. Soc.73, 3174 (1951).

    Article  Google Scholar 

  37. J.A. Montgomery andC. Temple, Jr.,Synthesis of Potential Anticancer Agents. XXVI. The Alkylation of 6-Chloropurine, J. Am. Chem. Soc.83, 630 (1961).

    Article  Google Scholar 

  38. J.L. Turk,Delayed Hypersensitivity (North-Holland Publishing Company, Amsterdam 1967).

    Google Scholar 

  39. R.T. McCluskey, B. Benacerraf andJ.W. McCluskey,Studies on the Specificity of the Cellular Infiltrate in Delayed Hypersensitivity Reactions, J. Immun.90, 466 (1963).

    PubMed  Google Scholar 

  40. B.R. Bloom,In vitro Approaches to the Mechanism of Cell-Mediated Immune Reactions, Adv. Immun.13, 101–208 (1971).

    PubMed  Google Scholar 

  41. E.R. Hurd andM. Ziff,Studies on the Anti-Inflammatory Action of 6-Mercaptopurine, J. exp. Med.128, 785 (1968).

    Article  PubMed  Google Scholar 

  42. A.R. Page, R.M. Condie andR.A. Good,Effect of 6-Mercaptopurine on Inflammation, Am. J. Path.40, 519 (1962).

    PubMed  Google Scholar 

  43. J.E. Stevens andD.A. Willoughby,The Anti-Inflammatory Effect of some Immunosuppressive Agents, J. Path.97, 367 (1969).

    Article  PubMed  Google Scholar 

  44. D.A. Clarke, F.S. Philips, S.S. Sternberg, C.C. Stock, G.B. Elion andG.H. Hitchings,6-Mercaptopurine: Effects in Mouse Sarcoma 180 and in Normal Animals, Cancer Res.13, 593 (1953).

    PubMed  Google Scholar 

  45. F.S. Philips, S.S. Sternberg, L. Hamilton andD.A. Clarke,The Toxic Effects of 6-Mercaptopurine and Related Compounds, Ann. N.Y. Acad. Sci.60, 283 (1954).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemical Pharmacology, The Squibb Institute for Medical Research, 08540, Princeton, New Jersey, USA

    R. J. Wojnar & R. J. Brittain

Authors
  1. R. J. Wojnar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. J. Brittain
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wojnar, R.J., Brittain, R.J. Substituted 9-benzyladenines: Inhibitors of inflammation associated with the delayed hypersensitivity skin reaction. Agents and Actions 5, 152–160 (1975). https://doi.org/10.1007/BF02027357

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02027357

Keywords

Search

Navigation