通过全合成发现强效细胞迁移抑制剂：来自(+)-迁移他汀构效关系研究的经验教训。

Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin.

作者信息

Njardarson Jón T, Gaul Christoph, Shan Dandan, Huang Xin-Yun, Danishefsky Samuel J

机构信息

Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.

出版信息

J Am Chem Soc. 2004 Feb 4;126(4):1038-40. doi: 10.1021/ja039714a.

DOI:10.1021/ja039714a

PMID:14746469

Abstract

Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.

摘要

高活性的基于米格拉他汀的肿瘤迁移细胞抑制剂已成功合成。我们对米格拉他汀灵活且简洁的全合成使我们能够探索其他难以获得的米格拉他汀衍生结构基序。这一努力已导致发现了活性比天然产物高3个数量级的具有肿瘤细胞迁移抑制活性的类似物。