A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors

Barnes, Natalie G.; Parker, Anthony W.; Ahmed Mal Ullah, Amjed A.; Ragazzon, Patricia A.; Hadfield, John A.

Abstract

A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G2/M phase further confirming their ability to inhibit tubulin polymerisation.

Citation

Barnes, N. G., Parker, A. W., Ahmed Mal Ullah, A. A., Ragazzon, P. A., & Hadfield, J. A. (2020). A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors. Bioorganic and Medicinal Chemistry, 28(19), Article 115684. https://doi.org/10.1016/j.bmc.2020.115684

• Journal Article Type: Article
• Acceptance Date: Jul 27, 2020
• Online Publication Date: Aug 5, 2020
• Publication Date: Oct 1, 2020
• Publicly Available Date: May 26, 2023
• Journal: Bioorganic and Medicinal Chemistry
• Print ISSN: 0968-0896
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 19
• Article Number: 115684
• DOI: https://doi.org/10.1016/j.bmc.2020.115684
• Keywords: Combretastatin A-4TubulinCancerMicrotubules
• Publisher URL: https://doi.org/10.1016/j.bmc.2020.115684