Mimicking the biological activity of diazobenzo[ b]fluorene natural products with electronically tuned diazofluorene analogs

The synthesis, DNA cleaving, and anti-proliferative properties of electronically modulated diazofluorenes are reported. Under appropriate electronic modulation, simple diazofluorene analogs recapitulate the DNA cleavage activity of kinamycin D under thiol-based reducing conditions. Achieving DNA cle...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-10, Vol.16 (19), p.5148-5151
Main Authors: Zeng, Wei, Eric Ballard, T., Tkachenko, Alexander G., Burns, Virginia A., Feldheim, Daniel L., Melander, Christian
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Antiproliferative activity
Biological and medical sciences
Carbazoles - pharmacology
Cell Proliferation - drug effects
Diazofluorenes
DNA cleavage
DNA Damage - drug effects
Fluorenes - chemical synthesis
Fluorenes - pharmacology
General aspects
HeLa Cells
Humans
Kinamycins
Lomaiviticins
Medical sciences
Molecular Mimicry
Pharmacology. Drug treatments
Structure-Activity Relationship
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Summary:The synthesis, DNA cleaving, and anti-proliferative properties of electronically modulated diazofluorenes are reported. Under appropriate electronic modulation, simple diazofluorene analogs recapitulate the DNA cleavage activity of kinamycin D under thiol-based reducing conditions. Achieving DNA cleavage under these reducing conditions is key to anticancer activity, as the most active compound, 1-methoxydiazofluorene, inhibits the proliferation of HeLa cells.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.07.024