Is DNA Minor Groove Binding Crucial for Biological Activity of Triazoloacridinones with Cytotoxic and Antitumour Properties?

Triazoloacridinones (TA) are a class of antitumor agents including a new compound C-1305 now in preclinical trials. In this study, the ability of triazoloacridinones to DNA minor groove binding and relevance to biological activity was investigated, using fluorochrome displacement method. From selected seven triazoloacridinone derivatives, differing in chemical structures, as well as in cytotoxic and antitumour activities only four of them showed C50 parameters (stronger DNA-binders in the minor groove). Weak or lack of correlation between minor groove binding and cytotoxic activities, suggested that these modes of interaction do not play a major role in the mechanism of biological action of TA.