Azapsoralens and benzoazapsoralens as new potential photochemo-therapeutic agents

New bioisosters of psoralen, azapsoralens substituting the central benzene ring with a pyridine nucleus, were prepared. Preliminary studies on two of these compounds indicate that azapsoralens have photochemical and photobiological properties similar to those of psoralen. 4,4'-Dimethyl and 4,4',5'-trimethylazapsoralen effectively form a preliminary molecular complex with DNA undergoing intercalation inside the duplex macromolecule. These compounds photoconjugate covalently with DNA, forming furan-side monoadducts. It is also shown that 4.4'-dimethylazapsoralen forms interstrand crosslinks in DNA, although to a smaller extent than with psoralen. 4-4'-Dimethylazapsoralen irradiated in ethanolic solution undergoes rapid photodegradation. Lastly the two new compounds show marked antiproliferative activity on Ehrlich cells, while they do not show skin phototoxicity on guinea-pig skin. Benzoazapsoralens were also prepared. 4-Methylbenzoazapsiralen behaves as monofunctional photoreagent towards DNA.