Lactimidomycin, Iso-migrastatin and Related Glutarimide-Containing 12-Membered Macrolides Are Extremely Potent Inhibitors of Cell Migration

作者：Jianhua Ju, Scott R. Rajski, Si‐Kyu Lim, Jeong-Woo Seo, Noël R. Peters, F. Michael Hoffmann, Ben Shen · 发表于：Journal of the American Chemical Society · 年份：2009 · DOI：10.1021/ja808462p · 被引用次数：63 · 研究领域：Chemical Synthesis and Analysis、Click Chemistry and Applications、Cancer therapeutics and mechanisms

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.