Cyclic Carboxylic Anhydrides as New Reagents for Formation of Chromone Ring

Frasinyuk, M. S.; Bondarenko, S. P.; Gorbulenko, N. V.; Туров, А. В.; Khilya, V. P.

doi:10.1002/jhet.1721

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…This unusual behavior of chromones 2a or 2e toward hydroxylamine can be explained by the strong electron-withdrawing effect of the aza-heterocyclic moiety in position 3 of the chromone ring. The bearing of ω-carboxyalkyl group 3-hetarylchromones 6a – 6d and related 3-aryl-4-(2-benzothiazolyl)pyrazole 6e were synthesized as we have earlier reported [ 47 ] ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

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Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

et al. 2022

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Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.

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Section: Resultsmentioning

confidence: 99%

“…Compounds 1a [ 43 ], 1b [ 45 ], 1c [ 44 ], 1e [ 46 ], 2a [ 43 ], 2b [ 45 ], 2c [ 44 ], 2e [ 46 ], 3c [ 44 ], 6a – 6d [ 47 ], 8 [ 48 ], and 9a,b [ 49 ] were synthesized by procedures reported earlier.…”

Section: Methodsmentioning

confidence: 99%

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

et al. 2022

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“…401 The reaction of 1-(2,4-dihydroxyphenyl)-2-(4-chlorophenyl) ethan-1-one with acetic anhydride in triethylamine at 140 °Cf o l l o w e d by hydrolysis gave the corresponding 7-acetoxy-3-(4-chlorophenyl)-2methyl-4H-chromen-4-one. 402 Other 2-(ω-carboxyalkyl)-3-(hetero)aryl-4H-chromen-4-ones were synthesized via condensation reaction of 2-[(hetero)aryl]-1-(2-hydroxyaryl)ethan-1-ones with cyclic carboxylic anhydrides (succinic, glutaric and diglycolic) in dry pyridine at room temperature for 24 h 403 and with succinic, glutaric, diglycolic and 1,2cyclopropanedicarboxylic acid anhydrides in the presence of triethylamine and DBU in 1,4-dioxane, followed by acidification (Scheme 71). 404,405 5.6 Starting from α-diazo 1,3-diketones…”

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confidence: 99%