The synthesis of 4, 6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells. Issue 11 (1st June 2019)

• Record Type: Journal Article
• Authors: Ruparelia, Ketan C.; Lodhi, Sabahat; Ankrett, Dyan N.; Wilsher, Nicola E.; Arroo, Randolph R.J.; Potter, Gerard A.; Beresford, Kenneth J.M.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 11(2019)
• Page Start: 1403
• Page End: 1406
• Publication Date: 2019-06-01
• Subjects: 4, 6-Diaryl-2-pyridones -- Chalcones -- Antiproliferative -- Prodrug -- CYP1B1; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.03.030
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.