Work

Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

Year: 2013

Type: article

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.

Source: Chemical Science

DOI: 10.1039/c3sc50174d

Authors: Nicolas Boyer, Karen C. Morrison, Justin Kim, Paul J. Hergenrother, Mohammad Movassaghi

Institutions: Massachusetts Institute of Technology, University of Illinois Urbana-Champaign

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of General Medical Sciences