Anthrapyrazoles are DNA-intercalating agents that are currently being studied as less cardiotoxic alternatives to anthracycline-based anticancer drugs. A bisanthrapyrazole consists of two anthrapyrazoles linked by a molecular spacer arm. Entropic effects should favor intercalation of both anthrapyrazoles and thus increase their biological activity. Previous studies suggest that improving the water-solubility of bis-anthrapyrazoles should yet improve their bio-availability and hence their cytoxicity. This can be achieved by linking the anthrapyrazoles using a water-soluble polyglycolic spacer arm. In the present study, two such bis-anthrapyrazole derivatives were synthetized. One of them was prepared using three different coupling methods. In particular, one of the coupling methods proved very efficient and versatile to synthetize various bis-anthrapyrazole derivatives, together with saving several synthetic steps. The bisanthrapyrazole with a triglycolic spacer arm was successfully purified and sent for biological testing. The ability of the synthesized bisanthrapyrazoles to bis-intercalate into DNA is currently being estimated using molecular modeling.

Synthesis and molecular modeling of the DNA-binding ability of bisanthrapyrazoles with a polyglycolic spacer arm

243rd National Meeting (2012)

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