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,omega-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-(omega-bromoalkoxy)-9,10-anthraquinone. Ring-opening of the epoxide (5) or 1-hydroxy-3-(omega-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.
National University Kaohsiung, Kaohsiung, Taiwan, ROC.
B L
BL
Wei
S H
SH
Wu
M I
MI
Chung
S J
SJ
Won
C N
CN
Lin
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
D000880:Anthraquinones; D000970:Antineoplastic Agents