title: In vitro study of the photocytotoxicity of bathochromically-shifted hypericin derivatives.
abstract: 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.
authors.affiliation: Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Roelants
authors.forename: Bernd
authors.initials: B
authors.lastname: Lackner
authors.forename: Mario
authors.initials: M
authors.lastname: Waser
authors.forename: Heinz
authors.initials: H
authors.lastname: Falk
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
mesh_terms: D000042:Absorption; D000818:Animals; D000873:Anthracenes; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008027:Light; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D010569:Perylene; C004965:hypericin