Apoptolidin: Induction of apoptosis by a natural product

被引:99
作者
Daniel, PT
Koert, U [1 ]
Schuppan, J
机构
[1] Univ Marburg, D-35032 Marburg, Germany
[2] Humboldt Univ, Univ Med Ctr Charite, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany
[3] Chiracon GmbH, Biotechnol Pk, Luckenwalde, Germany
关键词
apoptosis; drug design; natural products; total synthesis;
D O I
10.1002/anie.200502698
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Apoptolidin is a natural product that selectively induces apoptosis in several cancer cell lines. Apoptosis, programmed cell death, is a biological key pathway for regulating homeostasis and morphogenesis. Apoptotic misregulations are connected with several diseases, in particular cancer. The extrinsic way to apoptosis leads through death ligands and death receptors to the activiation of the caspase cascade, which results in proteolytic degradation of the cell architecture. The intrinsic pathway transmits signals of internal cellular damage to the mitochondrion, which loses its structural integrity, and forms an apoptosome that initiates the caspase cascade. Compounds which regulate apoptosis are of high medical significance. Many natural products regulate apoptotic pathways, and apoptolidin is one of them. The known synthetic routes to apoptolidin are described and compared in this Review. Selected further natural products which regulate apoptosis are introduced briefly. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:872 / 893
页数:22
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