In vitro study of the photocytotoxicity of bathochromically-shifted hypericin derivatives

Hypericin has excellent photosensitizing properties and displays favorable tumouritropic characteristics, but at the same time exhibits minimal dark toxicity. As such, the compound is a promising photosensitizer in the context of clinical photodynamic therapy (PDT). The present study was undertaken...

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Published in:Photochemical & photobiological sciences 2009-06, Vol.8 (6), p.822-829
Main Authors: Roelants, Mieke, Lackner, Bernd, Waser, Mario, Falk, Heinz, Agostinis, Patrizia, Van Poppel, Hendrik, Witte, Peter A. M. de
Format: Article
Language:English
Subjects:
Absorption
Animals
Biochemistry
Biological Transport
Biomaterials
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Proliferation - radiation effects
Chemistry
Humans
Intracellular Space - metabolism
Light
Perylene - analogs & derivatives
Perylene - chemistry
Perylene - metabolism
Perylene - pharmacology
Perylene - toxicity
Photochemotherapy
Photosensitizing Agents - chemistry
Photosensitizing Agents - metabolism
Photosensitizing Agents - pharmacology
Photosensitizing Agents - toxicity
Physical Chemistry
Plant Sciences
Singlet Oxygen - metabolism
Spectrometry, Fluorescence
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Summary:Hypericin has excellent photosensitizing properties and displays favorable tumouritropic characteristics, but at the same time exhibits minimal dark toxicity. As such, the compound is a promising photosensitizer in the context of clinical photodynamic therapy (PDT). The present study was undertaken to investigate whether a newly-synthesized series of hypericin derivatives with a bathochromic shift shows promise for future PDT applications. Potentially these structures offer an advantage over the parent compound by being photo-activated by red light, which penetrates deeper into tumour tissue. Our results show that 3 compounds (a dibenzoxazole, a pyridazinone, and especially a dibenzthiazole derivative of hypericin), designed to exhibit a bathochromic shift in their absorption spectrum, demonstrated an efficient singlet oxygen yield and intracellular uptake, and concomitantly a potent photocytotoxic effect under white-light conditions. These results indicate that it is possible to synthesize bathochromically-shifted compounds based on hypericin chemistry which maintain their PDT potential. However, the data also show that the present derivatives are only poor photosensitizers when used under red-light conditions.
ISSN:1474-905X
1474-9092
DOI:10.1039/b820817d