Photobiological studies of new cyclopentene-psoralens

Psoralen analogues bearing a cyclopentane ring fused to either the 4',5' do uble bond (compound 4) or the 3,4 double bond (compound 7) of the tricyclic furocoumarin structure were prepared. AM1 theoretical calculations perform ed for these compounds indicated that the electronic properties of their re active double bonds were very similar to those of psoralen and its derivati ve 8-methoxypsoralen (8-MOP), though the overall molecular geometries were clearly different, particularly as regards the change in molecular curvatur e produced by the introduction of the cyclopentane ring. Compound 4 showed a capacity similar to that of 8-MOP to inhibit the growth of human cervix a denocarcinoma cells (HeLa) and to induce mutagenic effects, but it was defi nitely less phototoxic to skin than 8-MOP. Its ability to photoadd to DNA a nd to cross-link DNA strands was also demonstrated. Instead. compound 7 was practically devoid of biological activity and no interaction with the macr omolecule could be detected. These differences in behaviour between 4 and 7 are probably due to the molecular curvature resulting fi om the introducti on of the cyclopentane ring. (C) 1998 Elsevier Science S.A. All rights rese rved.