Synthesis and Biological Activities of Topopyrones

Paul A. Zaleski†, Rumit Maini†‡, Simon J. Leiris†, Mark A. Elban§, and Sidney M. Hecht*†‡

†Center for BioEnergetics, Biodesign Institute, and ‡Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-6301, United States

§ Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States

J. Nat. Prod., Article ASAP

DOI: 10.1021/np200777z

Publication Date (Web): March 30, 2012

Structure–activity studies were employed to investigate the stabilization of DNA–topoisomerases I and II covalent binary complexes by topopyrone analogues. The synthesis of five new topopyrone derivatives and study of their ability to stabilize DNA–topoisomerase I and DNA–topoisomerase II covalent binary complexes are described. The biochemical assays suggest that the orientation of the fused 1,4-pyrone ring and halogen substituents contribute importantly to the overall potency of the topopyrones as topoisomerase poisons.

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