1,3-Dihydroxy-9,10-anthraquinone (4) was reacted with epichlorohydrin or 1,
omega -dibromo-alkane to yield 1-hydroxy-3-(2,3-epoxypropoxy)-9, 10-anthraq
uinone (5) and 1-hydroxy-3-(3-chloro-2-hydroxypropoxy) (6) or 1-hydroxy-3-(
omega -bromoalkoxy)-9,10-anthraquinone. Ring-opening of the epoxide (5) or
1-hydroxy-3-(omega -bromoalkoxy)-9,10-anthraquinones with appropriate amine
s, afforded various 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthra
quinones. The synthetic compounds were tested in vitro inhibition of human
T-24, Hep 3B, Hep G2, SiHa, HT-3, PLC/PRF/5 and 212 cells. Almost all compo
unds showed significant inhibitory activity against several different cance
r cell lines. Structure-activity analysis indicated epoxidation of the hydr
oxyanthraquinone increased cytotoxicity against tumour cells, but ring-open
ing of the epoxide group with amine did not enhance the cytotoxic activity.
The phosphatidylserine (PS) externalization and DNA fragmentation in SiHa
cells were significantly observed after 48 h incubation with selected compo
und 19. The results show that 19 cause cell death by apoptosis. (C) 2000 Ed
itions scientifiques et medicales Elsevier SAS.