Synthesis of Novel Topopyrones and Evaluation of Their Topoisomerase Poisoning Activity

Abstract

The topopyrones are a class of polycyclic molecules which act as topoisomerase poisons. Several novel derivatives have been synthesized, highlighting interesting ring formation reactions. These derivatives were tested for topoisomerase poisoning activity in vitro and compared quantitatively. Results have shed light on the relationship between structure and function in these molecules. The positioning of a halide substituent in linear and angular topopyrones has different effects on the activity of each group of molecules. In addition, it was shown that phenolic groups cause the compounds to act as poisons better than methoxy substituents. The new information found here may serve as a basis for developing more potent topopyrones, and also adds to the synthetic organic chemist’s list of techniques.