Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Winterbourne Botanic Garden
- X-ray Crystallography Facility
- ApconiX Ltd
- Institute for Cancer and Genomic Sciences, University of Birmingham, College of Medical and Dental Sciences, Birmingham, B152TT, UK.
- Liverpool John Moores University
Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from feverfew and protocols for growing, extracting and derivatising it are reported. A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on in vitro anti-leukaemic activity and calculated “drug-likeness” properties, in vitro and in vivo pharmacokinetics studies and hERG liability testing. In vitro studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative. The newly identified compound was shown to have pro-oxidant activity and in silico molecular docking studies indicate a prodrug mode of action. A synthesis scheme is presented for the production of amine 7 used in the generation of 5f.
|Number of pages||12|
|Publication status||Published - 1 Aug 2019|