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Issue 4, 2013
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Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

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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.

Graphical abstract: Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

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The article was received on 04 Dec 2012, accepted on 21 Jan 2013 and first published on 24 Jan 2013

Article type: Edge Article
DOI: 10.1039/C3SC50174D
Chem. Sci., 2013,4, 1646-1657

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    Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

    N. Boyer, K. C. Morrison, J. Kim, P. J. Hergenrother and M. Movassaghi, Chem. Sci., 2013, 4, 1646
    DOI: 10.1039/C3SC50174D

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