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

  • Bioorg Med Chem Lett. 2019 Jun 1;29(11):1403-1406. doi: 10.1016/j.bmcl.2019.03.030.
Ketan C Ruparelia  1 ,  Sabahat Lodhi  1 ,  Dyan N Ankrett  1 ,  Nicola E Wilsher  1 ,  Randolph R J Arroo  1 ,  Gerard A Potter  1 ,  Kenneth J M Beresford  2
Affiliations
  • 1. Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK.
  • 2. Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK. Electronic address: [email protected].
PMID: 30935796 DOI: 10.1016/j.bmcl.2019.03.030
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.

Keywords
4,6-Diaryl-2-pyridones; Antiproliferative; CYP1B1; Chalcones; Prodrug.