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Angew Chem Int Ed Engl. 2014 Aug 25;53(35):9325-8. doi: 10.1002/anie.201404137. Epub 2014 Jul 9.

Analysis of diazofluorene DNA binding and damaging activity: DNA cleavage by a synthetic monomeric diazofluorene.

Author information

1
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-8107 (USA) http://www.chem.yale.edu/herzongroup.

Abstract

The lomaiviticins and kinamycins are complex DNA damaging natural products that contain a diazofluorene functional group. Herein, we elucidate the influence of skeleton structure, ring and chain isomerization, D-ring oxidation state, and naphthoquinone substitution on DNA binding and damaging activity. We show that the electrophilicity of the diazofluorene appears to be a significant determinant of DNA damaging activity. These studies identify the monomeric diazofluorene 11 as a potent DNA cleavage agent in tissue culture. The simpler structure of 11 relative to the natural products establishes it as a useful lead for translational studies.

KEYWORDS:

DNA cleavage; DNA damage; cancer; natural products

PMID:
25044348
PMCID:
PMC4206835
DOI:
10.1002/anie.201404137
[Indexed for MEDLINE]
Free PMC Article

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