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Novel phototherapeutic agents: Investigation and progress of hypocrellin derivatives

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Chinese Science Bulletin

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.

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References

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

    Article  Google Scholar 

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

    Google Scholar 

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

    Article  Google Scholar 

  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.

    Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Google Scholar 

  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.

    Article  Google Scholar 

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

    Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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Authors and Affiliations

  1. Center for Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, 100080, Beijing, China

    Shangjie Xu, Shen Chen, Manhua Zhang & Tao Shen

  2. Department of Chemical Engineer, Harbin Engineering University, 150001, Harbin, China

    Xiaoxing Zhang & Zhengping Wang

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  1. Shangjie Xu
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  2. Xiaoxing Zhang
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  3. Shen Chen
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  4. Manhua Zhang
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  5. Tao Shen
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  6. Zhengping Wang
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Correspondence to Xiaoxing Zhang.

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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

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  • DOI: https://doi.org/10.1007/BF03184053

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