4-Hydroxymethyl- and 4-methoxymethylfuro[2,3-h]quinolin-2(1H)-ones: synthesis and biological properties.
4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ) was prepared by a new profitable way, which allowed to synthesize also 4-methoxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (MOFQ), and 4-hydroxymethyl-6,8-dimethylfuro[2,3-h]quinolin-2(1H)-one (HOHFQ). Some biological activities of the three compounds were studied in comparison with 8-MOP. In the dark, they inhibited topoisomerase II, leading to a moderate antiproliferative activity in mammalian cells. The antiproliferative activity was also tested upon UVA irradiation in mammalian cells: all compounds showed higher activity than 8-MOP, without mutagenicity and skin phototoxicity, with the best results for HOFQ. Photobinding to DNA was investigated, demonstrating a different sequence specificity for these furoquinolinones in comparison with furocoumarins. For all these features, HOFQ and the other analogues appeared very promising photochemotherapeutic agents, whose mechanism of action will be further investigated.
Chilin
Adriana
A
Department of Pharmaceutical Sciences, University of Padova, Via Francesco Marzolo 5, I-35131, Padova, Italy. adriana.chilin@unipd.it
Marzano
Cristina
C
Baccichetti
Francarosa
F
Simonato
Morena
M
Guiotto
Adriano
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor; D002417:Cattle; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010777:Photochemistry; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
C450158:4-hydroxymethyl-1,6,8-trimethylfuro(2,3-h)quinolin-2(1H)-one; C478518:4-methoxymethylfuro(2,3-h)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005663:Furans; D007202:Indicators and Reagents; D009153:Mutagens; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; D004247:DNA