Synthesis and evaluation of ether-linked demethylepipodophyllotoxin dimers

A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lendi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-12, Vol.24 (24), p.5627-5629
Main Authors: Dunlap, Norma, Salyard, Tracy L J, Pathiranage, Anuradha Liyana, Stubblefield, Jeannie, Pitts, Steven L, Ashley, Rachel E, Osheroff, Neil
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - chemistry
Antigens, Neoplasm - metabolism
Cell Line, Tumor
Cell Survival - drug effects
Dimerization
DNA - chemistry
DNA - metabolism
DNA Cleavage - drug effects
DNA Topoisomerases, Type II - chemistry
DNA Topoisomerases, Type II - metabolism
DNA, Single-Stranded - chemistry
DNA, Single-Stranded - metabolism
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Ether - chemistry
Humans
Podophyllotoxin - chemical synthesis
Podophyllotoxin - chemistry
Podophyllotoxin - toxicity
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Summary:A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human topoisomerase IIα.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2014.10.082