Skip to main content

Research Repository

Advanced Search

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.

Authors

Natalie G. Barnes

Anthony W. Parker

Amjed A. Ahmed Mal Ullah

John A. Hadfield



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