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Derivatisation of Parthenolide to Address Chemoresistant Chronic Lymphocytic Leukaemia

submitted on 28.01.2019 and posted on 28.01.2019 by Xingjian Li, Daniel Payne, Badarinath Ampolu, Nicholas Bland, Jane T Brown, Mark Dutton, Catherine Fitton, Abigail Guliver, Lee Hale, Daniel Hamza, Geraint Jones, Rebecca Lane, Andrew Leach, Louise Male, Elena Merisor, Michael Morton, Alex Quy, Ruth Roberts, Rosanna Scarll, Timothy Schulz-Utermoehl, Tatjana Stankovic, Brett Stevenson, John Fossey, Angelo Agathanggelou
A protocol for growing, extracting and derivatising parthenolide obtained from feverfew varieties is reported. Aminated parthenolide derivatives were prepared via 1,4-addition of primary or secondary amines utilising established and modified methods. The parthenolide derivatives’ drug-likeness properties were computed and they were screened for anti-leukaemic activity against the TP53-mutant, chemo-refractory, MEC1 chronic lymphocytic leukaemia (CLL) cell line. A screening cascade identified a small number of the most active compounds and their properties, including in vivo pharmacokinetics and in vitro hERG liability, were compared against DMAPT. This cascade culminated in the identification of a new compound with good anti CLL activity, with fewer drawbacks than some headline compounds from the literature and with utility against drug-resistant disease. Literature precedent and molecular docking studies support a multi-target-driven mode of action.


MRC Confidence in Concepts at University of Birmingham

EPSRC internally allocated pump-priming fund at University of Birmingham


Royal Society Industry Fellowship (2012/R1)

EPSRC (EP/J003220/1)

University of Birmingham Postgraduate Studentship

Bloodwise (14031)


Email Address of Submitting Author


University of Birmingham


United Kingdom

ORCID For Submitting Author


Declaration of Conflict of Interest

Ruth Roberts and Michael J. Morton are co-founders and co-directors of Apconix Ltd, an integrated toxicology and ion channel company that provides expert advice on nonclinical aspects of drug discovery and drug development to academia, industry and non-for-profit organisations. The remaining authors declare no competing interests.