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

1,3-Dihydroxy-9,10-anthraquinone ( 4) was reacted with epichlorohydrin or 1,ω-dibromo-alkane to yield 1-hydroxy-3-(2,3-epoxypropoxy)-9,10-anthraquinone ( 5) and 1-hydroxy-3-(3-chloro-2-hydroxypropoxy)-9,10-anthraquinone ( 6) or 1-hydroxy-3-(ω-bromoalkoxy)-9,10-anthraquinone. Ring-opening of the epoxide ( 5) or 1-hydroxy-3-(ω-bromoalkoxy)-9,10-anthraquinones with appropriate amines, afforded various 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinones. 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 compounds showed significant inhibitory activity against several different cancer cell lines. Structure–activity analysis indicated epoxidation of the hydroxyanthraquinone increased cytotoxicity against tumour cells, but ring-opening 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 compound 19. The results show that 19 cause cell death by apoptosis.