Photochemotherapy of skin-diseases: comparative studies on the photochemical and photobiological properties of various mono- and bifunctional agents.

The antiproliferative activity of the classic photochemotherapeutic agents, that is bifunctional psoralens (8-methoxypsoralen, 8-MOP; 5-methoxypsoralen, 5-MOP; 4,5',8-trimethylpsoralen, TMP) as well as of those more recently proposed, that is, monofunctional furocoumarins (methylangelicins and 3-carbethoxypsoralen, 3-CPs) is ascribed to their capacity to photo-induce lesions in DNA. In this connection while bifunctional agents photo-induce both mono- and bifunctional (inter-strand cross-linkages) damages in the macromolecule both in vitro and in vivo, monofunctional furocoumarins photodamage DNA only through monofunctional lesions. To have a direct and precise comparison between the classic agents (8-MOP, 5-MOP, TMP) and those recently proposed (4,5'-dimethylangelicin, 4,5'-DMA; 3-CPs), we have made a comparative study of the capacity of the various compounds to form the dark complex with DNA as well as of their capacity to induce mono- and bifunctional damages in the macromolecule. A comparative study on the antiproliferative activity in terms of capacity to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells as well as of the capacity to inhibit epidermal DNA synthesis in mice is also reported. The emerging picture can give a precise comparison in terms of both photobinding to DNA, as well as antiproliferative and skin-phototoxic activities between the classic agents 8-MOP, 5-MOP, TMP and the new monofunctional agents 4,5'-DMA and 3-CPs.