The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells
Date
2019-03-22
Advisors
Journal Title
Journal ISSN
ISSN
0960-894X
Volume Title
Publisher
Elsevier
Type
Article
Peer reviewed
Yes
Abstract
As part of a programme to develop anticancer prodrugs which are activated by cytochrome P450 (CYP)1B1, a library of 4,6-diaryl-2-pyridones was synthesised in yields of 6-60% from the corresponding chalcones. A number of these derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing little toxicity towards a non-tumour breast cell line with no CYP expression. Metabolism studies provided evidence supporting the involvement of CYP1 enzymes in the bioactivation of these compounds.
Description
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
Keywords
4,6-diaryl-2-pyridones, chalcones, antiproliferative, prodrug, CYP1B1
Citation
Ruparelia, K.C., Lodhi, S., Ankrett, D.N., Wilsher, N.E., Arroo, R.R.J., Potter, G.A., Beresford, K.J.M. (2019) The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells. Bioorganic & Medicinal Chemistry Letters, 29 (11), pp. 1403-1406