Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids
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Movassaghi_Synthesis and.pdf
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Author(s)
Boyer, Nicolas Cedric
Morrison, Karen C.
Kim, Justin
Hergenrother, Paul J.
Movassaghi, Mohammad
Date Issued
January 2013
Journal
Chemical Science
Publisher
Royal Society of Chemistry, The
Citation
Boyer, Nicolas, Karen C. Morrison, Justin Kim, Paul J. Hergenrother, and Mohammad Movassaghi. “Synthesis and Anticancer Activity of Epipolythiodiketopiperazine Alkaloids.” Chemical Science 4, no. 4 (2013): 1646.
Version
Author's final manuscript
Abstract
The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction of dozens of ETP derivatives. The evaluation of these compounds against cancer cell lines in culture allows for the first expansive structure–activity relationship (SAR) to be defined for monomeric and dimeric ETP-containing natural products and their synthetic cognates. Many ETP derivatives demonstrate potent anticancer activity across a broad range of cancer cell lines and kill cancer cells via induction of apoptosis. Several traits that bode well for the translational potential of the ETP class of natural products include concise and efficient synthetic access, potent induction of apoptotic cell death, activity against a wide range of cancer types, and a broad tolerance for modifications at multiple sites that should facilitate small-molecule drug development, mechanistic studies, and evaluation in vivo.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1039/c3sc50174d
