Pyrroloquinolinone methylderivatives, furocoumarin analogues: synthesis and biological activity.
Searching new photochemotherapeutic agents, a series of methylpirroloquinolinones were prepared by a new synthetic pathway, thus univocally obtaining the title compounds. The photobiological activity of some of these compounds was assayed; upon UVA activation, a marked capacity of inhibiting macromolecular synthesis in Ehrlich cells was observed, which appeared to be markedly high testing protein synthesis. Pyrroloquinolinones induced a strong inhibition of the clonal growing capacity of HeLa cells cultivated in vitro. Studying DNA photodamage in HL60 cells high amounts of single strand breaks and DNA-protein cross-links were detected. Pyrroloquinolines inhibited T2 bacteriophage infectivity, but induced no significant amounts of revertants in E. coli WP2 TM9, a strain very sensitive to DNA damage. On the contrary, 8-MOP, tested in the same experimental conditions exhibited an evident photomutagenecity. These data suggest that pyrroloquinolines induced antiproliferative effects by a mechanism in which DNA-photobinding practically does not takes place, and therefore different from that shown by known furocoumarins. Pyrroloquinolinones showed also a moderate antiproliferative activity in the dark.
Rodighiero
P
P
Department of Pharmaceutical Sciences, Padova University, Italy.
Chilin
A
A
Manzini
P
P
Castellin
A
A
Guiotto
A
A
Bordin
F
F
Carlassare
F
F
Marzano
C
C
Baccichetti
F
F
D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis
D011564:Furocoumarins; D017319:Photosensitizing Agents; D015363:Quinolones; D012313:RNA; D004247:DNA