Skip to main content
Article
Identification of Anziaic Acid, a Lichen Depside from Hypotrachyna sp., as a New Topoisomerase Poison Inhibitor
Department of Chemistry and Biochemistry
  • Bokun Cheng, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York
  • Shugeng Cao, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts
  • Victor Vasquez, Unidad Estrategica de Bioprospeccion, Instituto Nacional de Biodiversidad (INBio) and Escuela de Quı´mica, Universidad de Costa Rica, San Jose´, Costa Rica
  • Thirunavukkarasu Annamalai, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York ; Department of Chemistry and Biochemistry, Florida International University, Miami, Florida
  • Giselle Tamayo-Castillo, Unidad Estrategica de Bioprospeccion, Instituto Nacional de Biodiversidad (INBio) and Escuela de Quı´mica, Universidad de Costa Rica, San Jose´, Costa Rica,
  • Yuk-Ching Tse-Dinh, New York Medical College, Valhalla, New York; Department of Chemistry and Biochemistry, Florida International University, Miami, Florida
Date of this Version
4-8-2013
Document Type
Article
Abstract

Topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate DNA cleavage complex formed by the topoisomerase enzymes, which trigger cell death. Here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the DNA cleavage complex formed by recombinant Yersinia pestistopoisomerase I as part of a larger effort to identify new antibacterial compounds. Further characterization and fractionation of the screening positives from the primary assay led to the discovery of a depside, anziaic acid, from the lichen Hypotrachyna sp. as an inhibitor for both Y. pestis and Escherichia colitopoisomerase I. In in vitro assays, anziaic acid exhibits antibacterial activity against Bacillus subtilis and a membrane permeable strain of E. coli. Anziaic acid was also found to act as an inhibitor of human topoisomerase II but had little effect on human topoisomerase I. This is the first report of a depside with activity as a topoisomerase poison inhibitor and demonstrates the potential of this class of natural products as a source for new antibacterial and anticancer compounds.

Comments

This article was originally published in PLoS One.

Creative Commons License
Creative Commons Attribution 2.0
Citation Information
Cheng B, Cao S, Vasquez V, Annamalai T, Tamayo-Castillo G, et al. (2013) Identification of Anziaic Acid, a Lichen Depside from Hypotrachyna sp., as a New Topoisomerase Poison Inhibitor. PLoS ONE 8(4): e60770. doi:10.1371/journal.pone.0060770