Synthesis and evaluation of antimigratory and antiproliferative activities of lipid-linked [13]-macro-dilactones

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 18; pp. 5472 - 5476
• Main Authors: Magpusao, Anniefer N., Desmond, Richard T., Billings, Katelyn J., Fenteany, Gabriel, Peczuh, Mark W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.09.2010; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cancer; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; General aspects; Glucosides - chemical synthesis; Glucosides - chemistry; Glucosides - pharmacology; Humans; Inhibitors; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Lipids - chemistry; Macro-dilactones; Medical sciences; Migrastatin; Neoplasms - drug therapy; Octyl glucoside; Pharmacology. Drug treatments; Structure-Activity Relationship; Migrastatin; Cell growth; Octyl glucoside; Inhibitors; Cell migration; Macro-dilactones; Antineoplastic agent; Human; Aldose; Glucoside; Cytotoxicity; Antimetastatic agent; Oxygen heterocycle; In vitro; Macrolide; Cell line; Structure activity relation; Bicyclic compound; Glycoside; Mammary gland; Chemical synthesis; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.07.083

The biological activities of a family of novel, lipid-linked 13-membered-ring macro-dilactones are reported. These [13]-macro-dilactones were synthesized by diacylation of functionalized diols, followed by ring-closing metathesis under conditions we had previously reported. Antimigratory, cytostatic and cytotoxic activities of the compounds against cancer cells were evaluated. Compound 13 was the most potent in the series, while compound 10 had the broadest concentration range of subtoxic antiproliferative activity. These compounds share common structural components, namely the [13]-macro-dilactone templated by an octyl α-glucoside 4,6-diol.