The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells

[Display omitted] 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 activitie...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2019-06, Vol.29 (11), p.1403-1406
Main Authors: Ruparelia, Ketan C., Lodhi, Sabahat, Ankrett, Dyan N., Wilsher, Nicola E., Arroo, Randolph R.J., Potter, Gerard A., Beresford, Kenneth J.M.
Format: Article
Language:English
Subjects:
4,6-Diaryl-2-pyridones
Antiproliferative
Chalcones
CYP1B1
Prodrug
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Summary:[Display omitted] 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2019.03.030