2,6-Dimethyl-9-methoxy-4H-pyrrolo [3,2,1-ij]quinolin-4-one, a new compound with unusual photosensitizing properties

Autor: Francarosa Baccichetti, Christine Marzano, Franco Bordin, Adriana Chilin, Paolo Rodighiero, F. Carlassare, Andrea Guiotto
Rok vydání: 1994
Předmět:
Zdroj: Journal of Photochemistry and Photobiology B: Biology. 24:101-108
ISSN: 1011-1344
DOI: 10.1016/1011-1344(94)07011-3
Popis: Some photobiological properties of 2,6-dimethyl-9-methoxy-4H-pyrrolo [3,2,1-ij]quinolin-4-one (PQ) have been studied in comparison with 8-methoxypsoralen (8-MOP). In Ehrlich cells, PQ induced a moderate inhibition in DNA 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, PQ also affected protein synthesis. Likewise marked antiproliferative effects were also observed in the study of the clonal growth of CHO cells cultivated in vitro . Using alkaline elution and CHO cells, a moderate formation of single-strand breaks (SSBs) and of DNA-protein cross-links (DPCs) was observed by incubation in the dark; upon UVA irradiation the amount of both lesions increased greatly, whereas no inter-strand cross-links (ISCs) were formed. As expected, 8-MOP did not damage DNA in the dark, but induced SSBs, ISCs and DPCs in the presence of UVA. The induction of SSBs by both compounds seems to be directly related to a photochemical event rather than to incisions during DNA repair. As the induction of ISCs, and also the formation of DPCs by 8-MOP and UVA, 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 seems to involve photosensitization by free PQ molecules connected with SSB and DPC formation rather than with a DNA photo-binding activity. The PQ activity observed in the dark could probably be ascribed to a moderate inhibition of topoisomerases.
Databáze: OpenAIRE