Dual Inhibition of both DNA Topoisomerases I and II by Novel Topopyrone Analogs

Arizona State University (AzTE)
posted on 06/03/2009

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Invention Description
DNA topoisomerases (I and II) have proven to be excellent targets for anti-cancer drug development, and, if fact, there are a number of topoisomerase I and topoisomerase II specific drugs currently on the market. Given that both enzymes are good targets, it would be desirable to have a single compound that inhibited both. Such a molecule might have an improved safety profile relative to the combination of two inhibitors that are used in clinical practice today.
The limiting toxicities of sequential or simultaneous combinations of topoisomerase I and II poisons can include severe to life-threatening neutropenia and anemia. This suggests the need for a novel anti-cancer agent that exhibit improved anti-topoisomerase activity with decreased toxic side effects.
Scientists at Arizona State University’s Biodesign Institute have developed a series of anti-cancer agents based on a topopyrone scaffold that simultaneously inhibit both topoisomerase I and II.
In vitro studies not only display specificity for both topoisomerases, but demonstrate effectiveness at significantly lower concentrations than current topoisomerase inhibitors. This suggests that more effective cancer therapy could be achieved with these compounds at lower doses, leading to less severe side effects than observed with current compounds.

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