去氢骆驼蓬碱在秀丽隐杆线虫体内代谢研究

发布时间：2018-05-06 14:21

本文选题：去氢骆驼蓬碱 + 秀丽隐杆线虫　；参考：《质谱学报》2017年04期

【摘要】：去氢骆驼蓬碱是一种β-咔啉类生物碱,能够显著地抑制秀丽隐杆线虫let-60(n1046gf)的多产卵器表型,具有治疗胰腺癌的潜在能力。本研究采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-QTOF MS)法分析去氢骆驼蓬碱,确定其可能的裂解途径及特征碎片离子,同时研究其单体在线虫体内的代谢产物,并对给药后不同时间点的线虫成虫体内去氢骆驼蓬碱的含量进行半定量分析。结果显示,去氢骆驼蓬碱的裂解途径主要为RDA裂解,包括甲基、羟基等基团的丢失以及吲哚环的开裂。在电喷雾正离子模式下,检测到去氢骆驼蓬碱(m/z213)的去甲基化(m/z199)、羟基化(m/z229)的代谢产物。半定量分析结果表明:0~5h,线虫代谢旺盛,线虫体内去氢骆驼蓬碱的含量下降约80%;5h后,代谢速率减慢。该方法适用于去氢骆驼蓬碱在线虫体内代谢产物的研究,能够为去氢骆驼蓬碱治疗胰腺癌的新药研发提供数据支持。
[Abstract]:Dehydrocamperine is a 尾 -carboline alkaloid, which can significantly inhibit the phenotype of ovipositor of Let-60n1046gf. it has the potential to treat pancreatic cancer. In this study, ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS) was used to determine the possible cleavage pathway and characteristic fragment ions, and to study the metabolites of its monomers in vivo. The content of dehydroharmine in adult nematodes at different time points after administration was analyzed by semi-quantitative analysis. The results showed that the cleavage pathway of dehydroharmine was mainly RDA cleavage, including the loss of methyl and hydroxyl groups and the cracking of indole ring. In the electrospray positive ion mode, the metabolites of demethylated m / z _ (213) and hydroxylated m / z _ (229) were detected. The results of semi-quantitative analysis showed that the metabolism of nematode was exuberant at 5 h, and the content of dehydroharmine in nematode decreased about 80 h and decreased after 5 h, and the metabolic rate slowed down. This method is suitable for the study of metabolites of dehydroharmine in vivo and can provide data support for the development of new drugs for the treatment of pancreatic cancer.
【作者单位】：北京中医药大学;
【基金】：北京中医药大学校级课题(2016-JYB-QNJSZX003)资助
【分类号】：O657.63;R285

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