大黄酸-雌激素偶联物的合成及其药理学活性

目的:设计并合成大黄酸-雌激素偶联物,以期在保留雌激素对骨的作用的同时降低其对子宫内膜增殖的刺激。方法:经雌酚酮或雌二醇3-位酚羟基以烷基哌嗪或聚乙二醇哌嗪为桥合成与大黄酸相连的衍生物,通过MS,1HNMR,IR确定结构,并研究目标化合物对小鼠子宫内膜增殖的影响、对体外培养小鼠胚胎长骨生长的影响。结果:合成的10个目标化合物中,部分目标物能促进体外培养小鼠胚胎长骨的生长,桥链为乙基或丙基时,化合物的活性较雌酚酮相比减弱,当桥链为三聚乙二醇时,对骨的促生长活性增强。所测定的目标物均未对小鼠显示出刺激子宫内膜增殖的作用。结论:大黄酸-雌激素偶联物保留了雌激素对骨的作用,且降低了其对子宫内膜增殖的刺激作用。

Preparation and characterization of N-octyl-N'-succinyl chitosan as a tumour-targeting carrier

Aim:To design and synthesize the estrogen-rhein hybrid compounds to decrease the simulating effect of estrgen on endometrium and maintaining the effect on bone. Methods:The compounds that link rhein to estrone or estadiol respectively through ethyl-piperazinyl,propyl-piperazinyl,butyl-piperazinyl,diethylene glycol-piperazinyl and triethylene glycol-piperazinyl were synthesized. The structures of these compounds were confirmed by MS,1H NMR and IR. The effects of target compounds that link rhein to estrone on long bones of fetal mice in vitro and on the endometrium of mice in vivo were studied. Results:Ten target compounds were synthesized.Some target compounds showed the activity of enhancing long bone growth in fetal mouse in vitro. The activity of the compound was lower than estrone when it was linked to ethyl-piperazinyl or propyl-piperazinyl,and stronger than estrone when it was linked to triethylene glycol-piperazinyl. No activity of stimulating proliferation in endometrium was observed in all the target compounds. Conclusion:The results suggested that the beneficial influence on the bone of estrogen has been remained and the side effects on endometrium have been decreased in these rhein-estrogen synthesized.