Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Novel phototherapeutic agents: Investigation and progress of hypocrellin derivatives

  • 33 Accesses

  • 9 Citations

Abstract

Hypocrellins, as a kind of novel phototherapeutic agents, have several advantages over the clinically used hematoporphyrin derivatives, including high-excited triplet state yield, high phototoxicity, low dark toxicity, and rapid metabolism. However, they exhibit little absorption in the photodynamic window (600–900 nm) and are not water soluble, which limits their application in photodynamic therapy. Sulfonated and metal-ioned hypocrellins have been designed and synthesized to improve their water solubility. Unfortunately, the water-soluble derivatives obtained exhibit lower photodynamic activity than the parent hypocrellins. Thiolated and aminated hypocrellins have also been designed and synthesized to enlarge their photoresponse. Among them, the aminated hypocrellins possess the highest photodynamic activity. We recently have further designed and synthesized some amphiphilic aminated hypocrellin derivatives. Thus, not only the photoresponse but also the water solubility is enhanced. The experimentsin vitro andin vivo on the derivatives are under way at present.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Dougherty, T. J., Gomer, C. J., Henderson, B. W. et al., Photodynarmc therapy, J. Natl. Cancer. Inst., 1998, 90: 889.

  2. 2.

    Spikes, J., Photosensitization, The Science of Photobiology, 2nd ed. (ed. Smith, K. C.), New York: Plenum Press, 1989, 79.

  3. 3.

    Amagasa, J., Dye blinding and photodynamic action, Photochem. Photobiol., 1981, 33: 947–955.

  4. 4.

    Foote, C. S., Type I and Type II mechanisms of photodynamic action, light-Activated Pesticides (ed. Heitz, J. R.), Washington D C: American Chemical Society, 1987, 22.

  5. 5.

    Moan, J., Properties for optimal PDT sensitizers, J. Photochem. Photobiol. B: Biol., 1990, 5: 521.

  6. 6.

    Athar, M., Elmets, C. A., Bickers, D. R. et al., A novel mechanism for the generation of Superoxide anions in hematoporphyin derivative-mediated cutaneous photosensitization activation of the xanthine oxidase pathway, J. Clin. Invest., 1989, 83: 1137.

  7. 7.

    Henderson, R. W., Dougherty, T. J., How does photodynamic therapy work? Photochem. Photobiol., 1992, 55: 145.

  8. 8.

    Vaux, D. L., Strasser, A., The molecular biology of apoptosis, Proc. Natl. Acad. Sci. USA, 1996, 93: 2239–2244.

  9. 9.

    Samali, A., Gorman, A. M., Cotter, T. G., Apoptosis-the story so far, Expenentia, 1996, 52: 933–941.

  10. 10.

    Webber, J., Luo, Y., Crilly, R. et al., An apoptoxtic reponse to photodynamic therapy with endogenous protoporphyrinin vivo, J. Photochem. Photobiol. B: Biol., 1996, 35: 209–211.

  11. 11.

    He, X. Y., Strikes, R. A., Thomson, S. et al., Photodynamic therapy with Photofrin II induces programmed cell death in carcinoma cell lines, Photochem. Photobiol., 1994, 59: 468–473.

  12. 12.

    Luo, Y., Kessel, D., Initiation of apoptosis versus necrosis by photodynamic therapy with chloroaluminum phthalocyanine, Photochem. Photobiol., 1997, 66: 479–483.

  13. 13.

    Svaasand, L. O., Optical Dosimetry for Direct and Interstitial Photoradiation Therapy of Malignant Tumors, New York: Alan R Liss, 1984.

  14. 14.

    Wilson, B. C., Jeeves, W. P., Lowe, D. M.,In vivo and post mortem measurements of the attenuation spectra of light in mammalian tissues, Photochem. Photobiol., 1985, 42: 153–162.

  15. 15.

    Henderson, B. W., Dougherty, T. J., Photodynamic Therapy: Basic Principles and Clinical Applications, New York: Marcel Dekker, 1992.

  16. 16.

    Brown, S. B., Vernon, D. I., Holroyd, J. A., Pharmacokinetics of Photofrin in Man, Photodynamic Therapy and Biomedical Lasers (eds. Spinelli, P., Dal, F. M., Marchesi, R.), London: Excerpta Medica, 1992, 475–479.

  17. 17.

    Zhao, K. H., Jiang, L. J., Conversion of hypocrellin A in alkaline and neutral media, Youji Huaxue (in Chinese), 1989, 9(3): 252–254.

  18. 18.

    Jiang, L. J., The structures, properties, photochemical reactions and reaction mechanisms of hypocrellin (I), Chin. Sci. Bull. (in Chinese), 1990, 35: 1608–1616.

  19. 19.

    Jiang, L. J., The structures, properties, photochemical reactions and reaction mechanisms of hypocrellin (II), Chin. Sci. Bull. (in Chinese), 1990, 35: 1681–1690.

  20. 20.

    Lown, J. W., Photochemistry and photobiology of perylenequinones, Can. J. Chem., 1997, 75: 99.

  21. 21.

    Diwu, Z. J., Lown, J. W., Hypocrellins and their uses in photosensitization, Photochem. Photobiol., 1990, 52: 609.

  22. 22.

    Diwu, Z. J., Novel therapeutic and diagnostic applications of hypocrellins and hypericins, Photochem. Photobiol., 1995, 61: 529.

  23. 23.

    Jiang, L. J., He, Y. Y., Photophysics, Photochemistry and Photobiology of hypocrellin photosensitizers, Chin. Sci. Bull., 2001, 46(1): 6–16.

  24. 24.

    Diwu, Z. J., Haugland, R. P., Liu, J. et al., Photosensitization by anticancer agents 21. new perylene and aminonaphthoquinones, Free Rad. Biol. Med., 1996, 20: 589–593.

  25. 25.

    Miller, G. G., Brown, K., Ballangrud, A. M. et al., Preclinical assessment of hypocrellin B and hypocrellin B derivatives sensitizers for photodynamic therapy of cancer: progress update, Photochem. Photobiol., 1997, 65: 714–722.

  26. 26.

    Diwu, Z. J., Lown, J. W., Phototherapeutic potential of alternative photosensitizers to porphyrins, Pharmacol. Ther., 1994, 63: 1–35.

  27. 27.

    Pang, S. Z., Qing, J. F., Yue, J. C. et al., Photosensitizing damage to morphology of Hela cells by bromide of hypocrellin B (5-Br-HB), Acta Biophys. Sin., 1994, 10: 651.

  28. 28.

    Yue, J. C., Pang, S. Z., Zhang, M. H. et al., Photodamage to hydroperitoneum hepatoma cells by hypocrellin derivatives (-ethanolamine), Acta Biophys. Sin. (in Chinese), 1994, 10: 485–492.

  29. 29.

    Zhang, W. G., Ma, L. P., Wang, S. W. et al., A novel photosensitizer, 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA). 1. synthesis of 2-BA-2-DMHA and its phototoxicity to MGC803 cells, J. Photochem. Photobiol. B: Biol., 1998, 44: 21.

  30. 30.

    Zhang, J., Cao, E. H., Li, J. F. et al., Photodynamic effects of hypocrellin A on three human malignant cell lines by inducing apoptotic cell death, J. Photochem. Photobiol. B: Biol., 1998, 43: 106.

  31. 31.

    Estey, E. P., Brown, K., Diwu, Z. J. et al., Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study, Cancer Chemother. Pharmacol., 1996, 37: 343–350.

  32. 32.

    Hudson, J. B., Zhou, J., Chen, J. et al., Hypocrellin, from Hypocrella bambuase, is phototoxic to human immunodeficiency virusm, Photochem. Photobiol., 1994, 60(3): 253–255.

  33. 33.

    Hudson, J. B., Imperial, V., Haugland, R. P. et al., Antiviral activities of photoactive perylenequinones, Photochem. Photobiol., 1997, 65: 352.

  34. 34.

    Diwu, Z. J., Zhang, C. L., Lown, J. W., Photosensitization with anticancer agents 13. The production of singlet oxygen by halogenated and metal-ion-chelated perylenequinones, J. Photochem. Photobiol. A: Chem., 1992, 66(1): 99–112.

  35. 35.

    Hu, Y. Z., An, J. Y., Jiang, L. J., Studies on the chelation of hypocrellin A with aluminium ion and the photodynamic action of the resulting complex, J. Photochem. Photobiol. B: Biol., 1994, 22: 219–227.

  36. 36.

    Diwu, Z. J., Lown, J. W., A simple high-yielding approach to perylenequinone from the novel one-step double coupling reaction of 1, 2-naphtoquinone, Tetrahedron, 1992, 48(1): 45–54.

  37. 37.

    Das, K., English, D. S., Petrick, J. W., Deutirium isotope effect on the excited-state photophysics of hypocrellin: evidence for proton or hydrogen atom transfer, J. Phys. Chem. A, 1997, 101: 3241.

  38. 38.

    English, D. S., Das, K., Ashby, G. A. et al., Confirmation of excited-state proton transfer and ground-state heterogeneity in hypericin by fluorescence upconversion, J. Am. Chem. Soc., 1997, 119(48): 11585.

  39. 39.

    English, D. S., Zhang, W., Kraus, G. A. et al., Excited-state photophysics of hypericin and its hexamethoxy analog: intramolecular proton transfer as a nonradiative process in hypericin, J. Am. Chem. Soc., 1997, 119(13): 2980.

  40. 40.

    Fehr, M. J., McCloskey, M. A., Petnch, J. W., Lightinduced acidification by the antiviral agent hypericin, J. Am. Chem. Soc., 1995, 117(6): 1833.

  41. 41.

    Jiang, Y., An, J. Y., Jiang, L. J., The photodynamic activity of bormated hypocrellins, Chin. Sci. Bull. (in Chinese), 1993, 38(9): 797–800.

  42. 42.

    Zhang, H. Y., Zhang, Z. Y., Wan, Q. et al., Protective effects of nonionic micelle on ground and excited states of hypocrellin B and its brominated products, Photographic Science and Photochemistry, 1996, 14(2): 138.

  43. 43.

    Zhao, H. X., Xu, Y. M., Zhang, Z. Y., The Raman spectroscopy of photosensitizing damage to DNA structure by hypocrellin B and its bromated derivatives, Chin. Sci. Bull., 1998, 43(9): 955–961.

  44. 44.

    Ma, J. H., Jiang, L. J., Photogeneration of singlet oxygen (1O2) and free radicals (Sen▪—, O 2 □— ) by tetra-brominated hypocrellin B derivative, Free Rad. Res., 2001, 35: 767–777.

  45. 45.

    Hu, Y. Z., An, J. Y., Jiang, L. J., Studies on the photoinduced sulfonation of hypocrellins, J. Photochem. Photobiol. A: Chem., 1993, 70: 301–308.

  46. 46.

    Hu, Y. Z., An, J. Y., Jiang, L. J., Photoinduced sulfonation of hypocrellins-effects of reaction conditions on the photosulfonation of hypocrellin B, Photographic Science and Photochemistry, 1995, 13(1): 35–41.

  47. 47.

    He, Y. Y., An, J. Y., Jiang, L. J., Glycoconjugated hypocrellin: Synthesis of [(β-D-glucosyl) ethylthiyl] hypocrellins and photosensitized generation of singlet oxygen, Biochim. Biophys. Acta, 1999, 1472: 232–239.

  48. 48.

    He, Y. Y., An, J. Y., Zou, W. et al., Photoreactions of hypocrellin B with thiol compounds, J. Photochem. Photobiol. B: Biol., 1998, 44: 45–52.

  49. 49.

    He, Y. Y., An, J. Y., Jiang, L. J., EPR and spectrophotometric studies on free radicals (O 2 □— , Cysa-HB▪—) and singlet oxygen (1O2) generated by irradiation of cysteamine substituted hypocrellin B, Int. J. Radiat. Biol., 1998, 74: 647–654.

  50. 50.

    He, Y. Y., An, J. Y., Jiang, L. J., Synthesis of a new water-soluble phototherapeutic sensitizer from hypocrellin B with enhanced red absorption, Dyes Pigments, 1999, 41: 93–100.

  51. 51.

    He, Y. Y., Jiang, L. J., Photosensitized damage to calf thymus DNA by a hypocrellin derivative: mechanisms under aerobic and anaerobic conditions, Biochim. Biophys. Acta, 2000, 1523(1): 29–36.

  52. 52.

    Hu, Y. Z., An, J. Y., Jiang, L. J., Studies of sulfonation of hypocrellin A and the photodynamic actions of the product, J. Photochem. Photobiol. B: Biol., 1993, 17(2): 195–201.

  53. 53.

    Song, Y. Z., An, J. Y., Jiang, L. J., ESR studies of the photodynamic properties of a long-wavelength and water soluble hypocrellin B derivative: photogeneration of semiquinone radical anion and activated oxygen, J. Photochem. Photobiol. A: Chem., 1999, 123(1): 39–46.

  54. 54.

    Tang, Y. J., Liu, H. Y., An, J. Y. et al., Synthesis, characterization and photodynamic acitivity of amino-substituted-hypocrellin derivatives, Photochem. Photobiol., 2001, 74: 773.

  55. 55.

    Li, L., Chen, Y. W., Shen, J. Q. et al., New long-wavelength perlenequinones: synthesis and phototoxicity of hypocrellin B derivatives, Biochim. Biophys. Acta, 2000, 1523: 6–12.

  56. 56.

    Xia, W. L., Zhang, M. H., Jiang, L. J., The reaction between hypocrellin B and ethanolamine, Youji Huaxue (in Chinese), 1992, 12(6): 618–623.

  57. 57.

    Xu, S. J., Chen, S., Zhang, M. H. et al., A novel method for the preparation of amino-substituted hypocrellin B, Bioorg. Med. Chem. Lett., 2001, 11(15): 2045–2047.

  58. 58.

    Yang, H. Y., Zhang, W. G., Ma, L. P. et al., An approach to enhancing the phototoxicity of novel hypocrellin congener to MGC803 cells, Dyes Pigments, 2001, 51: 103–110.

  59. 59.

    Zhang, W. G., Ma, L. P., Wang, S. W. et al., Antisense bcl-2 retrovirus vector increases the sensitivity of the human gastric adenocarcinoma cell line to photodynamic therapy, Photochem. Photobiol., 1999, 69(5): 582.

  60. 60.

    Xu, S. J., Chen, S., Zhang, M. H. et al., Butylamino-demethoxyhypocrellins and photodynamic therapy decreases human cancerin vitro andin vivo, Biochim. Biophys. Acta, 2001, 1537(3): 222–232.

  61. 61.

    Xu, S. J., Chen, S., Zhang, M. H. et al., Cyclohexylamino-demethoxy-hypocrellin B and photodynamic therapy decreases human cancerin vitro, Anti-Cancer Drug Des., 2001, 16(6): 271–277.

  62. 62.

    Diwu, Z. J., Lown, J. W., Photosensitization of anticancer agents. 12. Perylenequinonoid pigments, a novel type of singlet oxygen sensitizer, J. Photochem. Photobiol. A: Chem., 1992, 64(3): 273.

  63. 63.

    Yu, C. L., Xu, S. J., Chen, S. et al., Investigation of photobleaching of hypocrellin B in non-polar organic solvent and in liposome suspension, J. Photochem. Photobiol. B: Biol., 2002, 68(2): 73–78.

  64. 64.

    Wang, Z. J., He, Y. Y., Huang, C. G. et al., Pharmacokinetics, tissue distribution and photodynamic therapy efficacy of liposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy, Photochem. Photobiol., 1999, 70(5): 773.

Download references

Author information

Correspondence to Xiaoxing Zhang.

About this article

Cite this article

Xu, S., Zhang, X., Chen, S. et al. Novel phototherapeutic agents: Investigation and progress of hypocrellin derivatives. Chin.Sci.Bull. 48, 1775–1785 (2003). https://doi.org/10.1007/BF03184053

Download citation

Keywords

  • photodynamic therapy
  • EPR
  • hypocrellins
  • singlet oxygen
  • superoxide anion radical