Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration.

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.

• Authors: Jianhua Ju, Scott R Rajski, Si-Kyu Lim, Jeong-Woo Seo, Noël R Peters, F Michael Hoffmann, Ben Shen
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 131 Issue 4 Pg. 1370-1 (Feb 04 2009) ISSN: 1520-5126 [Electronic] United States
• PMID: 19132897 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biological Products
• Macrolides
• Piperidones
• isomigrastatin
• lactimidomycin
• glutarimide

Topics

• Animals
• Biological Products (chemistry)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Humans
• Macrolides (chemistry, pharmacology)
• Mice
• Molecular Structure
• Piperidones (chemistry, pharmacology)
• Structure-Activity Relationship