By the same authors

From the same journal

From the same journal

Synthesis of cytotoxic spirocyclic imides from a biomass-derived oxanorbornene

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)

Author(s)

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

Department/unit(s)

Publication details

JournalTetrahedron
DateAccepted/In press - 6 Nov 2020
DateE-pub ahead of print - 12 Nov 2020
DatePublished (current) - 1 Jan 2021
Volume77
Number of pages12
Early online date12/11/20
Original languageEnglish

Abstract

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).

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.

    Research areas

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

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations