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

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Jan 10

PMID 19132897

Citations 18

Authors

Jianhua Ju

Scott R Rajski

Si-Kyu Lim

Jeong-Woo Seo

Noel R Peters

F Michael Hoffmann

Ben Shen

Affiliations

Soon will be listed here.

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.

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