Photobiological properties of 1-(3 '-hydroxypropyl)-4,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one, a new furocoumarin analogue

A new furoquinolinone derivative, 1-(3'-hydroxypropyl)-4,6,8-trimethylfuro[ 2,3-h]quinolin-2(1H)-one (HPFQ, 4), was prepared, in which the nitrogen ato m in position 1 carries a hydroxypropyl chain. The antiproliferative activi ty of HPFQ was studied in comparison with its analogue 1,4,6, 8-tetramethyl furo[2, 3-h]quinolin-2(1H)-one (FQ) and g-methoxypsoralen (8-MOP). By incub ation in the dark. HPFQ, although retaining antitopoisomerase II activity, appeared less effective than FQ. Upon UVA irradiation, HPFQ produced little amounts of singlet oxygen, but detectable levels of superoxide anion; like FQ, HPFQ induced numbers of DNA-protein cross-links, but no interstrand cr oss-links in mammalian cells. The HPFQ phototoxicity was comparable to that of FQ and g-MOP, while mutagenic activity, scored in two Escherichia coli strains, seemed much less remarkable. (C) 2000 Elsevier Science S.A. All ri ghts reserved.