Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins
Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins
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DOI：
10.1016/j.bmc.2009.01.022
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Pichette, Andre
中科院分区：
文献类型：
--
作者：
Gauthier, Charles;Legault, Jean;Pichette, Andre
在包括人类在内的大多数动物中诱导毒性的红细胞溶血是皂苷作为抗肿瘤剂的临床开发的主要缺点。在这项研究中，溶血和细胞毒活性，以及膜细胞透化性能的31个半合成和天然羽扇烷和齐墩果烷型皂苷库进行了评价，并建立了构效关系。结果表明，羽扇豆烷型皂苷在测试的最大浓度（100 μ M）下不表现出任何溶血活性和膜细胞透化性质，与糖部分的性质无关。虽然齐墩果烷型皂苷如β-常春藤皂苷（25）和常春藤皂苷A（1）（27）通过透化细胞膜导致癌细胞系死亡，但羽扇烷型皂苷似乎通过另一种机制进行，这可能与诱导细胞凋亡有关。总之，结果表明，在C-3位带有α-L-吡喃鼠李糖部分的细胞毒性羽扇豆烷型糖苷10和22代表了用于对荷瘤小鼠进行进一步研究的有希望的抗肿瘤剂，因为它们没有与红细胞溶血相关的毒性。(C)2009爱思唯尔有限公司保留所有权利。
The haemolysis of red blood cells inducing toxicity in most animals including humans is a major drawback for the clinical development of saponins as antitumour agents. In this study, the haemolytic and cytotoxic activities as well as the membrane cell permeabilization property of a library of 31 semi-synthetic and natural lupane- and oleanane-type saponins were evaluated and the structure-activity relationships were established. It was shown that lupane-type saponins do not exhibit any haemolytic activity and membrane cell permeabilization property at the maximum concentration tested (100 mu M) independently of the nature of the sugar moieties. While oleanane-type saponins such as beta-hederin (25) and hederacolchiside A(1) (27) cause the death of cancer cell lines by permeabilizing the cellular membranes, lupane-type saponins seem to proceed via another mechanism, which could be related to the induction of apoptosis. Altogether, the results indicate that the cytotoxic lupane-type glycosides 10 and 22 bearing an alpha-L-rhamnopyranose moiety at the C-3 position represent promising antitumour agents for further studies on tumour-bearing mice since they are devoid of toxicity associated with the haemolysis of red blood cells. (C) 2009 Elsevier Ltd. All rights reserved.