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Photochemotherapy using pyridopsoralens.

L Dubertret, D Averbeck, E Bisagni

    Biochimie
    |March 1, 1985
    PubMed
    Summary
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    New psoralen derivatives, pyrido (3,4-C) psoralen (PP) and 7-methyl pyrido (3,4-C) psoralen (MPP), show reduced mutagenicity per cell compared to 8-MOP, offering potential for safer photochemotherapy.

    Area of Science:

    • Photochemistry
    • Molecular Biology
    • Dermatology

    Background:

    • Psoralen-UVA (PUVA) therapy is effective for skin conditions but has acute side effects and genotoxic risks.
    • There is a need for novel photosensitizers with improved safety profiles.
    • Pyrido psoralens (PP and MPP) were synthesized as potential alternatives to 8-MOP.

    Purpose of the Study:

    • To synthesize and evaluate pyrido psoralens (PP and MPP) for reduced genotoxicity and side effects compared to 8-MOP.
    • To assess their photophysical properties, DNA binding, and biological activities in yeast and mammalian cells.

    Main Methods:

    • Synthesis of PP and MPP.
    • Spectroscopic analysis (UVA absorption, photostability).
    • DNA complexation studies (fluorescence, denaturation-renaturation).

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  • Biological assays in yeast (lethal effects, mitochondrial damage, mutagenicity, recombination) and mammalian cells (DNA synthesis inhibition, mutagenicity, cell transformation, sister chromatid exchange induction).

    • Main Results:

    • PP and MPP exhibit UVA absorption and photostability comparable to 8-MOP.
    • They form DNA adducts, primarily monoadditions, under UVA irradiation.
    • In yeast, PP and MPP are more effective than 8-MOP for lethal and mitochondrial damage but less mutagenic per viable cell.
    • In mammalian cells, MPP and PP show varying effectiveness in inhibiting DNA synthesis, inducing mutations, and transforming cells, generally showing higher activity than 8-MOP per unit dose but lower mutagenicity per viable cell.

    Conclusions:

    • Pyrido psoralens (PP and MPP) demonstrate potential as safer alternatives to 8-MOP in photochemotherapy.
    • They exhibit reduced mutagenicity per viable cell, particularly in yeast.
    • Further investigation is warranted to fully elucidate their therapeutic potential and safety profile.