Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cance...Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cancer, the results of the preliminary pharmacological screening showed that compound 6c, i.e. 17-(2'-oxazoly)-androsta-5,16-diene-3-ol was a strong inhibitor, comparable with that of the reference compound VN-85. The introduction ofmethyl or phenyl group at the 4' or 5' position of oxazole ring decreased the activity. The in vitro activities of 3- acetate 5a-c and 8 were lower than their 3-ol counterparts 6a-c and 9 as expected. The further pharmacological study of 6c is in progress.展开更多
文摘【目的】研究连翘叶提取物(Forsythia suspensa leaves extract,FSLE)对孕马血清促性腺激素(pregnant mare serum gonadotropin,PMSG)在肝脏中代谢的影响,改善在畜牧生产中因PMSG代谢缓慢而造成的氧化应激。【方法】采用半仿生酶醇法提取连翘叶有效成分,给予昆明雌鼠不同含量的FSLE进行动物体内试验;收集小鼠血清,进行酶联免疫吸附试验,检测各组小鼠血清中PMSG的质量浓度;采集小鼠肝脏组织,检测氧化应激指标谷胱甘肽、超氧化物歧化酶、丙二醛和过氧化氢的水平;采用Western-blot检测小鼠肝脏组织孕烷X受体(pregnane X receptor,PXR)和细胞色素酶P45017A1(cytochrome P45017A1,CYP17A1)蛋白的表达水平。【结果】FSLE可显著降低小鼠血清中PMSG的质量浓度,且可以减缓PMSG代谢引起的氧化应激。Western-blot结果显示:FSLE可显著下调小鼠肝组织中PXR和CYP17A1蛋白的表达。【结论】连翘叶提取物可能是通过下调肝脏中PXR和CYP17A1的表达减缓PMSG代谢引起的氧化应激。
文摘Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cancer, the results of the preliminary pharmacological screening showed that compound 6c, i.e. 17-(2'-oxazoly)-androsta-5,16-diene-3-ol was a strong inhibitor, comparable with that of the reference compound VN-85. The introduction ofmethyl or phenyl group at the 4' or 5' position of oxazole ring decreased the activity. The in vitro activities of 3- acetate 5a-c and 8 were lower than their 3-ol counterparts 6a-c and 9 as expected. The further pharmacological study of 6c is in progress.
