DNA damage and biological effects induced by photosensitization with new N(1)-unsubstituted furo[2,3-h]quinolin-2(1H)-ones.
New furoquinolinones unsubstituted at the N(1) position were prepared and their photobiological activities were studied in comparison with 4,6,8,9-tetramethylfuro[2,3-h]quinolin-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 DPC(L=0), but no ISC and DPC(L>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.
Department of Pharmaceutical Sciences, University of Padua, Via Francesco Marzolo 5, I-35131 Padova, Italy.
Cristina
C
Marzano
Adriana
A
Chilin
Franco
F
Bordin
Francarosa
F
Baccichetti
Adriano
A
Guiotto
D000818:Animals; D017122:Bacteriophage T4 / Q000187:drug effects / Q000254:growth & development / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004926:Escherichia coli; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects / Q000528:radiation effects; D009374:Neoplasms, Experimental / Q000473:pathology; D010787:Photosensitivity Disorders / Q000139:chemically induced; D017319:Photosensitizing Agents / Q000009:adverse effects* / Q000138:chemical synthesis / Q000633:toxicity; D015363:Quinolones / Q000009:adverse effects* / Q000138:chemical synthesis / Q000633:toxicity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D015363:Quinolones; D004247:DNA