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 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.
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References
Abdel-Rahman AH, Hammouda MAA, El-Desoky SI (2005) Synthesis of some new azole, azepine, pyridine, and pyrimidine derivatives using 6-Hydroxy-4H-4-oxo[1]-benzopyran-3-carboxaldehyde as a versatile starting material. Heteroat Chem 16:20–27. https://doi.org/10.1002/hc.20048
Bari A, Ali SS, Kadi A, Hashmi IA, Ng SW (2014) Synthesis of some new heterocyclic compounds derived from 3-formylchromones and their antimicrobial evaluation. Chem Heterocycl Compd 49:1723–1731. https://doi.org/10.1007/s10593-014-1424-4
Bari A, Parvez MK, Khan AA, Alanazi AM, Syed SA, Al-Dosari MS, Alobaid AM (2016) A facile one-pot synthesis and anticancer evaluation of novel substituted 1,2-dihydropyridine and 1,2,3,4-tetrahydropyrimidine analogues. J Heterocycl Chem 53:377–382. https://doi.org/10.1002/jhet.2400
Chand K, Alsoghier HM, Chaves S, Santos MA (2016) Tacrine-(hydroxybenzoyl-pyridone) hybrids as potential multifunctional anti-Alzheimer’s agents: aChE inhibition, antioxidant activity and metal chelating capacity. J Inorg Biochem 163:266–277. https://doi.org/10.1016/j.jinorgbio.2016.05.005
Gosh ChK, Ray A, Patra A (2001) Benzopyrans. Part 42 [1]. Reactions of 4-oxo-4H-1-benzopyran-3-carbaldehyde with some active methylene compounds in the presence of ammonia. J Heterocycl Chem 38:1459–1463. https://doi.org/10.1002/jhet.5570380632
Kováčiková L, Gašparová R, Boháč A, Ďurana M, Lácová M (2010) Synthesis of 3-phenyl-2H,5H-pyrano[3,2-c]chromen-2-one derivatives and their antineoplastic activity. ARKIVOC 11:188–203. https://doi.org/10.3998/ark.5550190.0011.b16
Lácova M, Loos D, Chovancová J, Králová K (1999, 2000) Phthalides and chromones from 4-coumarin acetic acids. Study of beneficial effects of microwave irradiation on synthesis. Electronic conference proceedings of ECSOC-3 and ECSOC-4, Sept. 1–30, 1999 and 2000:181–193. http://www.mdpi.org/ecsoc/ecsoc-3/a0039/a0039.htm (accessed 20nd April 2018)
Lácová M, Gašparová R, Koiš P, Boháč A, El-Shaaer HM (2010) A facile route to phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2-c]chromenes. Tetrahedron 66:1410–1419. https://doi.org/10.1016/j.tet.2009.11.057
Lv Z, Sheng C, Wang T, Zhang Y, Liu J, Feng J, Sun H, Zhong H, Niu C, Li K (2010) Design and synthesis of novel 2′-hydroxy group substituted 2-pyridone derivatives as anticancer agents. J Med Chem 53:660–668. https://doi.org/10.1016/j.ejmech.2013.06.046
Maezono SMB, Poudel TN, Xia L, Lee YR (2016) A green synthetic approach to synthesizing diverse 2-pyridones for their exceptional UV shielding functions. RSC Adv 6:82321–82329. https://doi.org/10.1039/C6RA18661K
Mehrparvar S, Balalaie S, Rabbanizadeh M, Ghabraie E, Rominger F (2014) An efficient tandem approach for the synthesis of functionalized 2-pyridone-3-carboxylic acids using three-component reaction in aqueous media. Mol Divers 18:535–543. https://doi.org/10.1007/s11030-014-9522-x
NCI search for all data by compound identifiers (2018) https://dtp.cancer.gov/dtpstandard/dwindex/index.jsp (accessed 28th April 2018)
NCI-60 human tumour cell lines screen (2018) https://dtp.cancer.gov/discovery_development/nci-60/default.htm (accessed 28th April 2018)
Nohara A, Ishiguro T, Sanno Y (1974) A novel conversion reaction of 4-oxo-4H-1-benzopyran-3-carbaldehydes to 3-substituted-5-(2-hydroxybenzoyl)-2(1H)-pyridones. Tetrahedron Lett 13:1183–1186. https://doi.org/10.1016/S0040-4039(01)82440-0
Poudel TN, Lee YR, Kim SH (2015) Eco-friendly synthesis of diverse and valuable 2-pyridones by catalyst- and solvent-free thermal multicomponent domino reaction. Green Chem 17:4579–4586. https://doi.org/10.1039/c5gc01526j
Rajkumar K, Suman P, Raju BCh (2015) Facile construction of novel heterocyclic compounds: three-component, one-pot synthesis of 2-hydroxybenzoyl-1,2-dihydropyridine-3-carboxylates, ketones, pyridone-3-carboxylates and benzopyrido-1,3-oxazole-4-carboxylates. RSC Adv 5:73850–73858. https://doi.org/10.1039/c5ra10185a
Ryabukhin SV, Plaskon AS, Volochnyuk DM, Tolmachev AA (2004) 3-Formylchromones in Guareschi Synthesis of 5-(2-Hydroxybenzoyl)-2-pyridones. Synlett 13:2287–2290. https://doi.org/10.1055/s-2004-832852
Sarma AK, Yadav P, Chand K, Sharma SK (2016) Design and synthesis of novel 2′-hydroxy group substituted 2-pyridone derivatives as anticancer agents. Indian. J. Chem Sec B 55B:492–500
SciFinder database https://scifinder.cas.org/scifinder/ (accessed 22nd April 2018)
NCI data search (2018) https://dtp.cancer.gov/dtpstandard/dwindex/index.jsp (accessed 28th April 2018)
Sengupta T, Gayen KS, Pandit P, Maiti DK (2012) FeCl3·6H2O-catalyzed intermolecular-cascade cyclization of acetoacetanilide: aldehyde-tuned synthesis to valuable 2-pyridone analogues. Chem Eur J 18:1905–1909. https://doi.org/10.1002/chem.201103354
The Compare Analysis https://dtp.cancer.gov/databases_tools/compare.htm (accessed 28th April 2018)
Zhang YK, Lv ZL, Niu CJ, Li K (2010) Synthesis and anti-HBV activity of novel 5-substituted pyridin-2(1H)-one derivatives. Chin Chem Lett 21:290–292. https://doi.org/10.1016/j.cclet.2009.10.010
Zhang Y, Lv ZL, Zhang M, Li K (2013) Re-cyclization of 3-(E)-methyl 3-(4-oxo-4H-chromen-3-yl)acrylate with amines and their potential mechanism. Tetrahedron 69:8839–8846. https://doi.org/10.1016/j.tet.2013.08.032
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).
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Matúš Čakurda importantly contributed to carrying out experiments and writing of this paper.
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Lácová, M., Čakurda, M., Koiš, P. et al. 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. Chem. Pap. 73, 55–69 (2019). https://doi.org/10.1007/s11696-018-0566-8
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DOI: https://doi.org/10.1007/s11696-018-0566-8