(-)-Roemerine, an aporphine alkaloid from Annona senegalensis that reverses the multidrug-resistance phenotype with cultured cells.
(-)-Roemerine, an aporphine alkaloid from Annona senegalensis that reverses the multidrug-resistance phenotype with cultured cells.
复制标题
DOI：
10.1021/np50118a021
复制
发表时间：
1995-04
影响因子：
5.1
通讯作者：
Min You;D. Wickramaratne;Gloria L. Silva;Heebyung Chai;T. Chagwedera;Norman R. Farnsworth;Geoffrey A. Cordell;A. Kinghorn;J. Pezzuto
中科院分区：
文献类型：
--
作者：
Min You;D. Wickramaratne;Gloria L. Silva;Heebyung Chai;T. Chagwedera;Norman R. Farnsworth;Geoffrey A. Cordell;A. Kinghorn;J. Pezzuto
从番荔枝叶中分离出的一种已知阿朴啡生物碱（-）-罗梅碱[1]，被发现可增强长春碱介导的多药耐药KB-V1细胞的细胞毒性反应。在不存在长春碱的情况下，用KB-3或KB-V1细胞未观察到显著的细胞毒性（ED 50> 20微克/ml），并且几种其他人肿瘤细胞系也相对不敏感。如其抑制ATP依赖性[3 H]长春碱与多药耐药KB-V1细胞膜囊泡结合的能力所示，（-）-罗梅碱似乎通过与P-糖蛋白相互作用发挥作用。除生物碱1外，还分离出三种非活性化合物[阿朴啡生物碱（-）-异紫堇定（首次报道为左旋构型）、木脂素（+/-）-8，8 '-bisdihydrosiringenin [2]（一种新的天然产物）和（+）-阿朴树脂素]。
A known aporphine alkaloid, (-)-roemerine [1], isolated from the leaves of Annona senegalensis, was found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB-V1 cells. In the absence of vinblastine, no significant cytotoxicity was observed with KB-3 or KB-V1 cells (ED50 > 20 micrograms/ml), and several other human tumor cell lines were also relatively insensitive. As indicated by its ability to inhibit ATP-dependent [3H]vinblastine binding to multidrug-resistant KB-V1 cell membrane vesicles, (-)-roemerine appears to function by interacting with P-glycoprotein. In addition to alkaloid 1, three inactive compounds [the aporphine alkaloid(-)-isocorydine (reported in the levo-configuration for the first time), and the lignans (+/-)-8,8'-bisdihydrosiringenin [2] (a new natural product), and (+)-syringaresinol] were also isolated.