Synthesis of cytotoxic spirocyclic imides from a biomass-derived oxanorbornene

Stefan B. Lawrenson, Amanda K. Pearce, Sam Hart, Adrian C. Whitwood, Rachel K. O'Reilly, Michael North*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


N-Substituted derivatives of cantharimide and norcantharimide represent a promising but underutilized motif for therapeutic applications. Herein, we report a divergent strategy for the preparation of secondary amides and norcantharimide-resembling spirocyclic imides from a biomass-derived oxanorbornene and assess their biological activity. Computational modelling suggests these compounds fall perfectly within lead-like chemical space (200 Da < RMM < 350 Da, −1 < AlogP < 3), with the spirocyclic imides preferred due to their lack of reactive functionalities. Biological analysis of the spirocyclic imides revealed that the compounds displayed antiproliferative activity against a range of human cancer cells (A549, HCT 116, OVCAR-3, MDA-MB-231, MCF7 and PC-3) with the N-octyl derivative displaying the greatest potential as a potent broad-spectrum anticancer drug. Dose-response curves for the N-octyl spirocyclic imide found EC50 values of 56–95 μM dependent on the cell line, with highest activity against human colorectal carcinoma cells (HCT 116).

Original languageEnglish
Article number131754
Number of pages12
Early online date12 Nov 2020
Publication statusPublished - 1 Jan 2021

Bibliographical note

© 2020 Elsevier Ltd. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy.


  • Active surfactants
  • Cantharidin
  • Cytotoxicity
  • Drug design
  • Spirocyclic

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