Sulphur and selenium analogues of psoralen as novel potential photochemotherapeutic agents.
Some heteropsoralens, obtained by replacing one or both the intracyclic oxygen atoms with sulphur and/or selenium, were studied. In preliminary tests, these compounds showed strong photobiological activity, in some cases more than two orders of magnitude higher than that of psoralen. Heteropsoralens containing sulphur undergo intercalation inside duplex DNA, showing evident affinity for the macromolecule; when selenium replaces furan oxygen, the psoralen isoster also undergoes intercalation but with lower efficiency, while psoralen isosters in which pyrone oxygen is replaced by selenium practically do not intercalate. Parallel behaviour was also observed for DNA photobinding and crosslink formation. The cycloadduct between furan selenium and pyrone sulphur isoster and thymine was isolated and characterized. The capacity of the various psoralen isosters to generate singlet oxygen and superoxide radical anion was studied. For the former the yield varies markedly for the various compounds, while for the latter the yield is similar for all compounds.
Vedaldi
D
D
Department of Pharmaceutical Sciences, University of Padova, Italy.
Caffieri
S
S
Frank
S
S
Dall'Acqua
F
F
Jakobs
A
A
Piette
J
J
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D003956:Dialysis; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006358:Hot Temperature; D011701:PUVA Therapy; D010777:Photochemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013455:Sulfur / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism
D003432:Cross-Linking Reagents; D011564:Furocoumarins; D017382:Reactive Oxygen Species; D013481:Superoxides; D013455:Sulfur; D004247:DNA; D012643:Selenium