A mild and efficient approach to the 6H-oxazolo[3,2-f]pyrimidine-5,7-dione scaffold via unexpected rearrangement of 2,3-dihydropyrimido[6,1-b][1,5,3]dioxazepine-7,9(5H,8H)-diones: synthesis, crystallographic studies, and cytotoxic activity screening

Mieczkowski, Adam; Bazlekowa, Milena; Bagiński, Maciej; Wójcik, Jacek; Winczura, Alicja; Miazga, Agnieszka; Ghahe, Somayeh Shahmoradi; Gajda, Roman; Woźniak, Krzysztof

doi:10.1016/j.tetlet.2016.01.006

Cited by 11 publications

(3 citation statements)

References 14 publications

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“…During our research on the design and discovery of novel anticancer compounds based on diverse heterocyclic structures, such as 6 H ‐oxazolo[3,2‐ f ]pyrimidine‐5,7‐dione, 47 1,3,4,12 a ‐tetrahydropyrazino[2,1‐ c ][1,4]benzodiazepine‐6,12(2 H ,11 H )‐dione, 48 as well as nucleoside derivatives 49–52 and natural poliphenolic compounds, 30 we turn our attention to halogenated flavonoid derivatives as possible ligands for tumor‐associated kinase CK2. The compounds used in this study are presented on Figure 1.…”

Section: Resultsmentioning

confidence: 99%

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

et al. 2020

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A series of halogenated derivatives of natural flavonoids: baicalein and chrysin were designed and investigated as possible ligands for the catalytic subunit of tumor-associated human kinase CK2. Thermal shift assay method, in silico modeling, and high-performance liquid chromatography-derived hydrophobicity together with IC 50 values determined in biochemical assay were used to explain the ligand affinity to the catalytic subunit of human protein kinase CK2. Obtained results revealed that substitution of baicalein and chrysin with halogen atom increases their binding affinity to hCK2α, and for 8-chlorochrysin the observed effect is even stronger than for the reference CK2 inhibitor-4,5,6,7-tetrabromo-1H-benzotriazole. The cytotoxic activities of the baicalein and chrysin derivatives in the in vitro model have been evaluated for MV4-11 (human biphenotypic B myelomonocytic leukemia), A549 (human lung adenocarcinoma), LoVo (human colon cancer), and MCF-7 (human breast cancer) as well as on the nontumorigenic human breast epithelial MCF-10A cell lines. Among the baicalein derivatives, the strongest cytotoxic effect was observed for 8-bromobaicalein, which exhibited the highest activity against breast cancer cell line MCF-7 (IC 50 10 ± 3 μM). In the chrysin series, the strongest cytotoxic effect was observed for unsubstituted chrysin, which exhibited the highest activity against leukemic cell line MV4-11 (IC 50 10 ± 4 μM). K E Y W O R D Sbaicalein, chromatographic hydrophobicity index, chrysin, CK2 kinase inhibition, cytotoxic effect, flavonoids, thermal shift assay Abbreviations: BSA, bovine serum albumin; DFT, discrete Fourier transform; DMSO, dimethyl sulfoxide; DSF, differential scanning fluorimetry; gHSQC, gradient heteronuclear single quantum correlation; hCK2α, catalytic subunit of human protein kinase CK2; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide;

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Section: Resultsmentioning

confidence: 99%

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

et al. 2020

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“…During our continuous efforts toward development of anticancer-relevant, heterocyclic derivatives [6][7][8], we investigated a reaction between 2-amino-5-bromobenzohydrazide 9, synthesized from 5-bromoisatoic anhydride and hydrazine hydrate according to the literature procedure [9], and methylphosphonyl dichloride 10 in the presence of triethylamine (Scheme 1). Equimolar amounts of 9 and 10 were dissolved in dry THF, three equivalents of triethylamine were added dropwise in room temperature and the reaction mixture was stirred in at room temperature for 18 h. Low-resolution mass spectrometry showed the formation of a new product with molecular mass M = 502 g/mol, and the isotopic profile revealed a product with two bromine atoms.…”

Section: Resultsmentioning

confidence: 99%

5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene

Kasperowicz

Czerwińska

Majchrzak

et al. 2018

Molbank

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5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ 5 -phosphaspiro [4.4]nona-2,7-diene was obtained by condensation of 2-amino-5-bromobenzohydrazide and methylphosphonyl dichloride in the presence of triethylamine. An initial biological screening was performed for the resulting product. The synthesized compound showed relatively strong cytotoxic activity, which was, however, similar for cancer and non-cancer cell lines.

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“…During our continuous efforts in the investigation of various heterocyclic derivatives as possible antiproliferative and potentially anticancer compounds [20][21][22], we decided to perform a reaction between 4,5-dimethyl-1,2-phenylenediamine (13) and N-(4-bromobenzyl)-3,1-benzoxazine-2,4-dione (N-(4-bromobenzyl)-isatoic anhydride) (14) in refluxing acetic acid (Scheme 2). We found only one example of a condensation involving of N-benzylated isatoic acid with 1,2-phenylenediamine in the literature [14], and decided to investigate this reaction as a possible pathway for the synthesis of complex, biologically-relevant compounds.…”

Section: Resultsmentioning

confidence: 99%

N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imid-azol-2-yl)benzeneamine

Dziełak

Trzybiński

Czerwińska

et al. 2018

Molbank

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N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)benzeneamine was obtained by condensation of N-(4-bromobenzyl)-3,1-benzoxazine-2,4-dione (N-(4-bromobenzyl)isatoic anhydride) with 4,5-dimethyl-1,2-phenylenediamine in refluxing acetic acid. This is a rare example of condensation of N-substituted 3,1-benzoxazine-2,4-dione with 1,2-phenylenediamine, which resulted in the formation of a benzimidazole derivative with a moderate yield. Crystallographic studies and initial biological screening were performed for the obtained product.

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A mild and efficient approach to the 6H-oxazolo[3,2-f]pyrimidine-5,7-dione scaffold via unexpected rearrangement of 2,3-dihydropyrimido[6,1-b][1,5,3]dioxazepine-7,9(5H,8H)-diones: synthesis, crystallographic studies, and cytotoxic activity screening

Cited by 11 publications

References 14 publications

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene

N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imid-azol-2-yl)benzeneamine

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