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
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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 3–5 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.
Keywords3-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
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).
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.
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