Wei B L, Wu S H, Chung M I, Won S J, Lin C N
National University Kaohsiung, Kaohsiung, Taiwan, ROC.
Eur J Med Chem. 2000 Dec;35(12):1089-98. doi: 10.1016/s0223-5234(00)01190-9.
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.
1,3 - 二羟基 - 9,10 - 蒽醌（4）与环氧氯丙烷或1,ω - 二溴代烷反应，生成1 - 羟基 - 3 - （2,3 - 环氧丙氧基）- 9,10 - 蒽醌（5）和1 - 羟基 - 3 - （3 - 氯 - 2 - 羟基丙氧基）- 9,10 - 蒽醌（6）或1 - 羟基 - 3 - （ω - 溴代烷氧基）- 9,10 - 蒽醌。环氧化合物（5）或1 - 羟基 - 3 - （ω - 溴代烷氧基）- 9,10 - 蒽醌与适当的胺进行开环反应，得到各种1 - 羟基 - 3 - （3 - 烷基氨基 - 2 - 羟基丙氧基）- 9,10 - 蒽醌。对合成的化合物进行了体外抑制人T - 24、Hep 3B、Hep G2、SiHa、HT - 3、PLC/PRF/5和212细胞的测试。几乎所有化合物对几种不同的癌细胞系都显示出显著的抑制活性。构效分析表明，羟基蒽醌的环氧化增加了对肿瘤细胞的细胞毒性，但环氧基团与胺的开环反应并未增强细胞毒性。用选定的化合物19孵育48小时后，在SiHa细胞中显著观察到磷脂酰丝氨酸（PS）外化和DNA片段化。结果表明，化合物19通过凋亡导致细胞死亡。
