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Chemical Papers

, Volume 73, Issue 1, pp 55–69 | Cite as

A novel and efficient synthesis of 3-aryl-5-(2-hydroxybenzoyl)pyridin-2(1H)-ones by re-cyclization of N-(oxopyranochromenyl)acetamides and their antineoplastic screening

  • Margita Lácová
  • Matúš Čakurda
  • Pavol Koiš
  • Gabriela Addová
  • Andrej BoháčEmail author
Original Paper
  • 32 Downloads

Abstract

We have developed a novel, simple and efficient methodology for preparation of yet unknown 3-aryl-5-(2-hydroxybenzoyl)pyridin-2(1H)-ones 3(a–g) by EtONa driven re-cyclization of N-(3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl)acetamides 2(a–g) in good yields (80–95%). A mechanism for this reaction was proposed. The 3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl acetates 1(a–g) were prepared by cyclocondensation from 3-formylchromones (4-oxo-4H-chromene-3-carbaldehydes) and acetic acids in 64–86% yields. Acetamides 2(a–g) were obtained by reaction of 3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl acetates 1(a–g) with AcNH2 catalyzed by pTsOH in 80–93% yields. Click chemistry precursors 4(a,d) and 5(a,d) were prepared by propargylation of 3(a,d) in 92–98% yields. They can serve for construction of more complex molecules possessing pyridone skeleton of 3. Eleventh novel compounds 3(a–g), 4(a,d) and 5(a,d) were screened on their anticancer activity on a panel of human tumour cell lines by NCI USA. We found that pyridones 35 selectively inhibit the growth of some of the tumour cell lines at 10−5 M (up to -33% compared to a control). The most sensitive tumour cell lines originated from kidney, breast, skin, ovary, blood and lung.

Graphical Abstract

Keywords

3-aryl-5-(2-hydroxybenzoyl)pyridin-2(1H)-ones N-(3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl)acetamides re-cyclization mechanism NCI tumour cell lines Click chemistry precursors 

Notes

Acknowledgements

This research was supported by the Biomagi, Ltd., NCI USA, VEGA 1/0670/18, Comenius University Science Park funded by the ERDF Grant no. ITMS 26240220086 (HPLC MS).

Author contribution

Matúš Čakurda importantly contributed to carrying out experiments and writing of this paper.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

11696_2018_566_MOESM1_ESM.docx (3.2 mb)
Supplementary material 1 (DOCX 3260 kb)

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Department of Organic Chemistry, Faculty of Natural SciencesComenius University in BratislavaBratislavaSlovakia
  2. 2.Institute of Chemistry, Faculty of Natural SciencesComenius University in BratislavaBratislavaSlovakia
  3. 3.Biomagi, LtdBratislavaSlovakia

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