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Synthesis and Biological Evaluation of Ether-Linked Derivatives of Phosphatidylinositol

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Abstract

The synthesis of two novel glycero-3-phosphoinositol ether lipid analogues, rac-l-O-octadecyl-2-O methylglycero-3-phospho-myo-inositol 6 (an ether lipid analogue of rac-l-O-octadecyl-2-O-methylglycero-3-phosphocholine; ET-18-OMe) and rac-l-O-octadecyl-2-O-acetylglycero-3-phospho-myo-inositol 11 (an ether lipid analogue of platelet-activating factor), is described. The two target compounds and the synthetic intermediates were evaluated for inhibition of HL60, BG1, and BG3 human malignant cells in vitro and inhibition of protein kinase C. Tumor inhibitory activity was found for compounds 6 and 11 in all systems but not for their synthetic intermediates. However, compounds 6 and 11 as well as the synthetic intermediates 5 and 13, but not 9, exhibited protein kinase C inhibitory activity.

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REFERENCES

  1. T.-C. Lee, and F. Snyder. In J. F. Kuo (ed.), Phospholipids and Cellular Regulation, CRC Press, Boca Raton, Fla., 1985, Vol. II, pp. 2–39.

    Google Scholar 

  2. W. E. Berdel, R. Andreesen, and P. G. Munder. In J. F. Kuo (ed.) Phospholipids and Cellular Regulation, CRC Press, Boca Raton, Fla., 1985, Vol. II, pp. 41–73.

    Google Scholar 

  3. W. E. Berdel and P. G. Munder. Antineoplastic actions of ether lipids related to platelet-activating factor. In F. Snyder (ed.), Platelet-Activiting Factor and Related Lipid Mediators, Plenum Press, New York, 1987, pp. 449–467.

    Google Scholar 

  4. E. J. Modest, L. W. Daniel, R. L. Wykle, M. E. Berens, C. Piantadosi, J. R. Surles, and S. Morris-Natschke. In K. Harrap and T. Connors (eds.), New Avenues in Developmental Cancer Chemotherapy, Bristol-Myers Cancer Symposia, Academic Press, New York, 1987, Vol. 8, pp. 387–400.

    Google Scholar 

  5. J. T. O'Flaherty, R. L. Wykle, C. H. Miller, J. C. Lewis, M. Waite, D. A. Bass, C. E. McCall, and L. R. DeChatelet. Am. J. Pathol. 103:70–78 (1981).

    Google Scholar 

  6. P. G. Munder, M. Modolell, W. Bausert, H. F. Oettgen, and O. Westphal. In E. M. Hersh, M. A. Chirigos, and M. J. Mastrangelo (eds.), Augmenting Agents in Cancer Therapy, Raven Press, New York, 1981, pp. 441–458.

    Google Scholar 

  7. D. N. Helfman, K. C. Baines, J. M. Kinkade, W. R. Vogler, M. Shoji, and J. F. Kuo. Cancer Res. 43:2955–2961 (1983).

    Google Scholar 

  8. J. Parker, L. W. Daniel, and M. Waite. J. Biol. Chem. 262: 5385–5393 (1987).

    Google Scholar 

  9. L. W. Daniel, L. A. Etkin, B. T. Morrison, J. Parker, S. Morris-Natschke, J. R. Surles, and C. Piantadosi. Lipids 22:851–855 (1987).

    Google Scholar 

  10. M. Modolell, R. Andreesen, W. Pahlke, U. Brugger, and P. G. Munder. Cancer Res. 39:4681–4686 (1979).

    Google Scholar 

  11. D. B. J. Herrmann. J. Natl. Cancer Inst. 75:423–430 (1985).

    Google Scholar 

  12. Y. Honma, T. Kasukabe, M. Hozumi, S. Tsushima, and H. Nomura. Cancer Res. 41:3211–3216 (1981).

    Google Scholar 

  13. G. Storme, W. E. Berdel, W. J. van Blitterswijk, E. A. Bruyneel, G. K. DeBruyne, and M. M. Mareel. Cancer Res. 45:351–357 (1985).

    Google Scholar 

  14. W. J. van Blitterswijk, H. Hilkmann, and G. A. Storme. Lipids 22:820–823 (1987).

    Google Scholar 

  15. A. Noseda, J. G. White, and E. J. Modest. Proc. Am. Assoc. Cancer Res. 28:13 (1987).

    Google Scholar 

  16. A. Noseda, P. L. Godwin, and E. J. Modest. Biochim. Biophys. Acta 945:92–100 (1988).

    Google Scholar 

  17. A. Noseda, J. G. White, P. L. Godwin, W. G. Jerome, and E. J. Modest. Exp. Mol. Pathol. (in press).

  18. A. Noseda, P. L. Godwin, and E. J. Modest. Proc. Am. Assoc. Cancer Res. 29:321 (1988).

    Google Scholar 

  19. S. Morris-Natschke, J. R. Surles, L. W. Daniel, M. E. Berens, E. J. Modest, and C. Piantadosi. J. Med. Chem. 29:2114–2117 (1986).

    Google Scholar 

  20. M. H. Marx, C. Piantadosi, A. Noseda, L. W. Daniel, and E. J. Modest. J. Med. Chem. 31:858–863 (1988).

    Google Scholar 

  21. A. Noseda, M. E. Berens, C. Piantadosi, and E. J. Modest. Lipids 22:878–883 (1987).

    Google Scholar 

  22. M. J. Berridge. Annu. Rev. Biochem. 56:159–193 (1987).

    Google Scholar 

  23. A. Kishimoto, Y. Takai, T. Mori, U. Kikkawa, and Y. Nishizuka. J. Biol. Chem. 255:2273–2276 (1980).

    Google Scholar 

  24. R. Gigg and C. D. Warren. J. Chem. Soc. C 2367–2371 (1969).

  25. A. Hermetter, F. Paltauf, and H. Hauser. Chem. Phys. Lipids 30:35–45 (1982).

    Google Scholar 

  26. S. S. Yang, T. R. Beattie, and T. Y. Shen. Tetrahedron Lett. 23:5517–5520 (1982).

    Google Scholar 

  27. J. R. Surles, R. L. Wykle, J. T. O'Flaherty, W. L. Salzer, F. Snyder, and C. Piantadosi. J. Med. Chem. 38:73–78 (1985).

    Google Scholar 

  28. B. A. Stoochnoff and N. L. Benoiton. Tetrahedron Lett. 1:21–24 (1973).

    Google Scholar 

  29. A. J. E. Porck and B. M. Craig. Can. J. Chem. 33:1286–1289 (1955).

    Google Scholar 

  30. E. J. Corey, J. L. Gras, and P. Ulrich. Tetrahedron Lett. 11: 809–812 (1976).

    Google Scholar 

  31. W. J. Baumann and H. K. Mangold. J. Org. Chem. 29:3055–3057 (1967).

    Google Scholar 

  32. C. E. Welander, T. M. Morgan, H. D. Homesley, P. P. Trotta, and R. J. Spiegel. Int. J. Cancer 35:721–729 (1985).

    Google Scholar 

  33. A. W. Hamburger and S. E. Salmon. Science 197:461–463 (1977).

    Google Scholar 

  34. R. W. Wilcox, R. L. Wykle, J. D. Schmitt, and L. W. Daniel. Lipids 22:800–807 (1987).

    Google Scholar 

  35. W. J. van Blitterswijk, R. L. van der Bend, I. J. M. Kramer, A. J. Verhoeven, H. Hilkmann, and J. de Witt. Lipids 22:842–846 (1987).

    Google Scholar 

  36. L. W. Daniel, G. W. Small, J. D. Schmitt, C. J. Marasco, K. S. Ishaq, and C. Piantadosi. Biochem. Biophys. Res. Commun. 151:291–297 (1988).

    Google Scholar 

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Author notes

  1. Alessandro Noseda

    Present address: “Mario Negri” Institute for Pharmacological Research, via Eritrea 62, 20157, Milan, Italy

Authors and Affiliations

  1. School of Pharmacy, Division of Medicinal Chemistry and Natural Products, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599

    Khalid S. Ishaq, Maria Capobianco & Claude Piantadosi

  2. Department of Biochemistry and Cancer, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina, 27103

    Alessandro Noseda, Larry W. Daniel & Edward J. Modest

Authors
  1. Khalid S. Ishaq
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  2. Maria Capobianco
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  3. Claude Piantadosi
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  4. Alessandro Noseda
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  5. Larry W. Daniel
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  6. Edward J. Modest
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Ishaq, K.S., Capobianco, M., Piantadosi, C. et al. Synthesis and Biological Evaluation of Ether-Linked Derivatives of Phosphatidylinositol. Pharm Res 6, 216–224 (1989). https://doi.org/10.1023/A:1015961416370

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