THYL-9-METHOXY-4H-PYRROLO[3,2,1-IJ]QUINOLIN-4-ONE, A NEW COMPOUND WITH UNUSUAL PHOTOSENSITIZING PROPERTIES

Some photobiological properties of ethyl-9-methoxy-4H-pyrrolo[3,2,1-ij ]quinolin-4-one (PQ) have been studied in comparison with 8-methoxypso ralen (8-MOP). In Ehrlich cells, PQ induced a moderate inhibition in D NA and RNA syntheses in the dark, which appeared to be more pronounced upon UVA irradiation. In contrast to 8-MOP, in the presence of UVA, P Q also affected protein synthesis. Likewise marked antiproliferative e ffects were also observed in the study of the clonal growth of CHO cel ls cultivated in vitro. Using alkaline elution and CHO cells, a modera te formation of single-strand breaks (SSBs) and of DNA-protein cross-l inks (DPCs) was observed by incubation in the dark; upon UVA irradiati on the amount of both lesions increased greatly, whereas no inter-stra nd cross-links (ISCs) were formed. As expected, 8-MOP did not damage D NA in the dark, but induced SSBs, ISCs and DPCs in the presence of WA. The induction of SSBs by both compounds seems to be directly related to a photochemical event rather than to incisions during DNA repair. A s the induction of ISCs, and also the formation of DPCs by 8-MOP and U VA, appears to be based on a two-step reaction involving photo-bound 8 -MOP-DNA moieties. In contrast, the formation of DPCs by PQ and UVA se ems to involve photosensitization by free PQ molecules connected with SSB and DPC formation rather than with a DNA photo-binding activity. T he PQ activity observed in the dark could probably be ascribed to a mo derate inhibition of topoisomerases.