Analysis of Diazofluorene DNA Binding and Damaging Activity: DNA Cleavage by a Synthetic Monomeric Diazofluorene

Authors：Woo Christina M; Ranjan Nihar; Arya Dev P; Herzon Seth B^*

Source：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53(35): 9325-9328.

DOI：10.1002/anie.201404137

• cancer
• DNA cleavage
• DNA damage
• natural products

The lomaiviticins and kinamycins are complexDNA 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.