摘要
目的:探讨七叶树皂苷和熊果酸及其衍生物对HIV-1蛋白酶活性的抑制作用,探讨构效关系。方法:采用体外实验法,将待测化合物、HIV-1蛋白酶基质与HIV-1蛋白酶在37℃共温育,根据HIV-1蛋白酶对其基质的水解强度计算待测化合物对HIV-1蛋白酶活性的抑制作用。结果:七叶树总皂苷、七叶树皂苷-Ia和七叶树皂苷-Ib混合物、异七叶树皂苷-Ia和异七叶树皂苷-Ib混合物、七叶树皂苷-Ia、全乙酰化七叶树皂苷-Ia、七叶树皂苷-Ib、熊果酸和乙酰熊果酸在100μmol.L-1浓度对HIV-1蛋白酶活性的抑制率分别为86%,89.9%,50.8%,100%,74.6%,89.3%,100%和100%。七叶树皂苷-Ia、全乙酰化七叶树皂苷-Ia、七叶树皂苷-Ib、熊果酸和乙酰熊果酸对HIV-1蛋白酶活性抑制作用的IC50分别为35,35,50,8和13μmol.L-1。阳性对照药乙酰胃酶抑素在本实验条件下的IC50为0.30μmo.lL-1。在100μmol.L-1浓度,七叶树皂苷-IVc,-IVd,-IVe,-IVf,异七叶树皂苷-Ia,-Ib,-IIa,-IIb,原七叶树皂苷元,21β-O-巴豆酰基原七叶树皂苷元,21β-O-当归酰基原七叶树皂苷元,2α-羟基熊果酸和委陵菜酸对HIV-1蛋白酶活性的抑制率<50%。结论:七叶树总皂苷、七叶树皂苷-Ia和七叶树皂苷-Ib混合物、异七叶树皂苷-Ia和异七叶树皂苷-Ib混合物、七叶树皂苷-Ia、全乙酰化七叶树皂苷-Ia、七叶树皂苷-Ib、熊果酸和乙酰熊果酸对HIV-1蛋白酶活性有抑制作用,最强者为七叶树皂苷-Ia、熊果酸和乙酰熊果酸。
Objective：To investigate inhibitory effect and structure-activity relationship of escins and ursolic acid derivatives against HIV-1 protease in vitro. Methods： The HIV-1 protease inhibition assay was performed in vitro by incubating tested compounds and substrates with HIV-1 protease at 37 ℃ for 15 min. The inhibitory activity was derived from the hydrolysis of HIV-1 protease to its substrates. Acetyl pepstatin with an IC50 of 0.3umol· L^ - 1 was used as a positive control. Results ： The inhibition percentage of total saponins from seeds of Aesculus chinensis, mixture of escins-Ⅰa and -Ⅰb, mixture of isoescins-Ⅰa and -Ⅰb, escin-Ⅰa, peracetylescin-Ⅰa, escin-Ⅰb, ursolic acid and acetylursolic acid at a concentration of 100umol·L^-1 against HIV-1 protease activity was 86% , 89.9% , 50.8% , 100% , 74.6% , 89.3% , 100% and 100%, respectively. IC50 value of escin-Ⅰa, peracetylescin-Ⅰa, escin-Ⅰb, ursolic acid and acetylursolic acid on HIV-1 protease activities was 35, 35, 50, 8 and 13umol· L^ -1 , respectively. At a concentration of 100 umol· L^-1, the inhibition percentage of escins-Ⅳc, -Ⅳd, -Ⅳe, -Ⅳf, isoescins Ⅰa,-Ⅰb, -Ⅱa, -Ⅱb, protoaescigenin, 21β-O-tigloylprotoaescigenin, 21β-O-angeloylprotoaescigenin, 2α-hydroxyursolic acid and tormentic acid was all below 50% , respectively. Conclusion： The total saponins of seeds of Aesculus chinensis, mixtures of escins-Ⅰa and -Ⅰb, mixtures of isoescins-Ⅰa and -Ⅰb, escin-Ⅰa, peracetylescin-Ⅰa, escin-Ⅰb, ursolic acid and acetylursolic acid were found to be inhibitory principles against HIV-1 protease activity. Escin-Ⅰa, ursolic acid and acetylursolic acid showed more potent activities.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第5期366-369,共4页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(29972004)
