New monofunctional reagents for DNA as possible agents for the photochemotherapy of psoriasis: derivatives of 4,5'-dimethylangelicin

With the aim of obtaining new agents for the photochemotherapy of psoriasis, we have prepared monofunctional reagents for DNA by starting from 4,5'-dimethylangelicin (2), an angular furocoumarin, and introducing in a 4'-(hydroxymethyl) (3), 4'-(methoxymethyl) (4), or 4'-(aminomethyl) group (5), in way analogous to what other authors have done previously on trioxsalen, a DNA bifunctional reagent. These new compounds form complexes with DNA in the ground state and by successive irradiation (UV-A) undergo monofunctional photoaddition to the macromolecule. Photobinding to DNA was highest for 3 and gradually lower for 4 and 5, respectively. These compounds do not form interstrand photocross-linkages in DNA and do not show any skin phototoxicity. Fluorimetric studies show that their 4',5' double bond is involved in the photoaddition to DNA. Their photobiological activity evaluated on Ehrlich ascites tumor cells and on T2 phages was strictly connected with their photobinding to DNA. The effect of the introduction of hydroxymethyl and methoxymethyl groups in angular 2 is somewhat similar to that previously described for trioxsalen: the introduction of an aminomethyl group in 2 markedly increases the affinity in the dark for DNA but under UV-A irradiation strongly inhibits photobinding to the macromolecule. By contrast, in the analogous derivative of trioxsalen both the affinity for DNA in the dark and the photobinding to DNA increased.