Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids
Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids
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DOI：
10.1016/j.bmc.2006.09.028
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Ferreira, Maria-Jose U.
中科院分区：
文献类型：
--
作者：
Duarte, Noelia;Varga, Andras;Ferreira, Maria-Jose U.
大环lathyrane二萜类化合物latilagascene D-F（1-3）和jolkinol B（4）是从大戟的甲醇提取物中分离得到的，并对小鼠淋巴瘤细胞的多药耐药性逆转活性进行了评价。与阳性对照维拉帕米相比，所有化合物均显示出非常强的活性。讨论了构效关系。还进行了从相同物种中分离的化合物1和4以及长萜A-C（5-7）作为骨化诱导剂的评价。化合物I是最活跃的。此外，在联合化疗的模型中，在体外对人MDR 1基因转染的小鼠淋巴瘤细胞研究了阿霉素和拉替拉加斯B（6）之间的相互作用，表明相互作用的类型是协同的。其中，黄曲霉素D-F（1-3）是一个新的化合物，其结构是根据波谱方法，包括2DNMR实验（COSY，HMQC，HMBC和NOESY）确定的。(c)2006爱思唯尔有限公司保留所有权利。
The macrocyclic lathyrane diterpenes, latilagascenes D-F (1-3) and jolkinol B (4), were isolated from the methanol extract of Euphorbia lagascae, and evaluated for multidrug resistance reversing activity on mouse lymphoma cells. All compounds displayed very strong activity compared with that of the positive control, verapamil. The structure-activity relationship is discussed. The evaluation of compounds 1 and 4, and of latigascenes A-C (5-7), isolated from the same species, as apoptosis-inducers was also carried out. Compound I was the most active. Furthermore, in the model of combination chemotherapy, the interaction between the doxorubicine and latilagascene B (6) was studied in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction was synergistic. Latilagascenes D-F (1-3) are new compounds whose structures were established on the basis of spectroscopic methods, including 2D NMR experiments (COSY, HMQC, HMBC and NOESY). (c) 2006 Elsevier Ltd. All rights reserved.