SULFUR AND SELENIUM ANALOGS OF PSORALEN AS NOVEL POTENTIAL PHOTOCHEMOTHERAPEUTIC AGENTS

Some heteropsoralens, obtained by replacing one or both the intracycli c oxygen atoms with sulphur and/or selenium, were studied. In prelimin ary tests, these compounds showed strong photobiological activity, in some cases more than two orders of magnitude higher than that of psora len. Heteropsoralens containing sulphur undergo intercalation inside d uplex DNA, showing evident affinity for the macromolecule; when seleni um replaces furan oxygen, the psoralen isoster also undergoes intercal ation but with lower efficiency, while psoralen isosters in which pyro ne oxygen is replaced by selenium practically do not intercalate. Para llel behaviour was also observed for DNA photobinding and crosslink fo rmation. The cycloadduct between furan selenium and pyrone sulphur iso ster and thymine was isolated and characterized. The capacity of the v arious psoralen isosters to generate singlet oxygen and superoxide rad ical anion was studied. For the former the yield varies markedly for t he various compounds, while for the latter the yield is similar for al l compounds.