乳酰亚胺霉素、异迁移他汀及相关含戊二酰亚胺的12元大环内酯类化合物是极其有效的细胞迁移抑制剂。
Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration.
作者信息
Ju Jianhua, Rajski Scott R, Lim Si-Kyu, Seo Jeong-Woo, Peters Noël R, Hoffmann F Michael, Shen Ben
机构信息
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705-2222, USA.
出版信息
J Am Chem Soc. 2009 Feb 4;131(4):1370-1. doi: 10.1021/ja808462p.
Abstract
Migrastatin (1), iso-migrastatin (5) and lactimidomycin (7) are all glutarimide-containing polyketides known for their unique structures and cytotoxic activities against human cancer cell lines. Migrastatin, a strong inhibitor of tumor cell migration, has been an important lead in the development of antimetastatic agents. Yet studies of the related 12-membered macrolides iso-migrastatin, lactimidomycin, and related analogues have been hampered by their limited availability. We report here the production, isolation, structural characterization, and biological activities of iso-migrastatin, lactimidomycin, and 23 related congeners. Our studies showed that, as a family, the glutarimide-containing 12-membered macrolides are extremely potent cell migration inhibitors with some members displaying activity on par or superior to that of migrastatin as exemplified by compounds 5, 7, and 9-12. On the basis of these findings, the structures and activity of this family of compounds as cell migration inhibitors are discussed.
摘要
迁移他汀（1）、异迁移他汀（5）和乳酰亚胺霉素（7）均为含戊二酰亚胺的聚酮化合物，以其独特的结构和对人类癌细胞系的细胞毒性活性而闻名。迁移他汀是肿瘤细胞迁移的强效抑制剂，一直是抗转移药物开发的重要先导化合物。然而，相关的12元大环内酯类化合物异迁移他汀、乳酰亚胺霉素及相关类似物的研究因它们的可得性有限而受到阻碍。我们在此报告异迁移他汀、乳酰亚胺霉素及23种相关同系物的制备、分离、结构表征及生物活性。我们的研究表明，作为一个家族，含戊二酰亚胺的12元大环内酯类化合物是极其有效的细胞迁移抑制剂，一些成员表现出与迁移他汀相当或优于迁移他汀的活性，如化合物5、7及9 - 12所示。基于这些发现，讨论了该类化合物作为细胞迁移抑制剂的结构与活性。
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Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration.乳酰亚胺霉素、异迁移他汀及相关含戊二酰亚胺的12元大环内酯类化合物是极其有效的细胞迁移抑制剂。
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