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.

doi:10.1016/j.bmc.2020.115684

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

Patricia Ragazzon p.ragazzon@keele.ac.uk

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.

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