Synthesis and cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives

Citation
Bl. Wei et al., Synthesis and cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives, EUR J MED C, 35(12), 2000, pp. 1089-1098
Citations number
23
Categorie Soggetti
Chemistry & Analysis
Journal title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
02235234 → ACNP
Volume
35
Issue
12
Year of publication
2000
Pages
1089 - 1098
Database
ISI
SICI code
0223-5234(200012)35:12<1089:SACEO1>2.0.ZU;2-X
Abstract
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.