DNA damage and biological effects induced by photosensitization with new N1-unsubstituted furo[2,3-h]quinolin-2(1H)-ones

New furoquinolinones unsubstituted at the N-1 position were prepared and their photobiological activities we re studied in comparison with 4.6.8.9-tetramethylfuro[2,3-h]quinotin-2(1H)-one (HFQ) and 8-MOP. The anti-proliferative activity of furoquinolinones 3a-f was tested upon UVA irradiation in mammalian cells, studying DNA synthesis and clonal growth capacity. and in micro-organisms, evaluating T2 infectivity. Almost all compounds appeared to be more active than 8-MOP, and free of any mutagenic activity and skin phototoxicity. Among them, compound 3b was the most effective one. Similarly to HFQ, compound 3b appeared to be very active also in DNA damaging, forming monoadducts and DPCL - 0. but no ISC and DPCL > 0, both responsible for furocoumarin genotoxicity and phototoxicity. Moreover, Ehrlich ascites cells, photoinactivated by the new furoquinolinone 3b and injected into recipient mice. proved to be capable of inducing protection against a successive challenge performed with the same tumor cells. For all these features. 3b seemed to be a new promising potential drug for PUVA therapy and photopheresis. (C) 2002 Elsevier Science Ltd. All rights reserved.