Bicyclic cytarabine analogues: synthesis and investigation of antitumor properties of novel, 6-aryl- and 6-alkyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one arabinosides

Mieczkowski, Adam; Makowska, Małgorzata; Sekuła, Justyna; Tomczyk, Ewelina; Zalewska, Ewa; Nasulewicz‐Goldeman, Anna; Wietrzyk, Joanna

doi:10.1016/j.tet.2015.09.015

Cited by 8 publications

(8 citation statements)

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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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“…According to the authors, the methoxy groups can be deprotected under acidic conditions. The intermediate can easily form the reactive dialdhyde which on reaction with amines can lead to pyrroles.Similarly, in 2015, Mieczkowski et al68 reported the reaction of 6-substituted furo[2,3d]pyrimidin-2(3H)-one arabinosides either with ammonium hydroxide at room temperature or with ammonia under microwave condition led to the fast removal of the acetyl groups followed by rather slow conversion of the deprotected furo[2,3-d]pyrimidin-2(3H)-one nucleosides to the 3H-pyrrolo[2,3d]pyrimidin-2(7H)-one nucleosides 66.…”

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confidence: 91%

Synthesis Strategies and Biological Value of Pyrrole and Pyrrolopyrimidine

Mohamed

El-Hameed

Sayed

2017

Journal of Advanced Pharmacy Research

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For several decades, interest in the synthesis pyrrole and pyrrolopyrimidine increases due to the importance of these heterocycles both from chemical and biological points of view. They possess several biological activities such as antimicrobial, analgesic, anti-inflammatory, anti-cancer, anti-viral, anti-convulsant, anti-hyperlipidemic, anti-depressant, antidiabetic, anti-allergic activities. These findings motivated us to present this review which highlights different methods of the synthesis of pyrrole and pyrrolopyrimidine derivatives as well as their biological importance from the past to recent years.

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“…Indeed, the tricyclic pyrrolo [1,4]benzodiazepine 1 exhibits a potent inhibition effect on the human DNA ligase (hLig1) [1]. Anticancer activity is also exhibited by the Diazepinomycin 2, a dibenzodiazepine derivative possessing a farnesyl residue and isolated from Micromonospora strain [2].…”

Section: Introductionmentioning

confidence: 99%

“…Anticancer activity is also exhibited by the Diazepinomycin 2, a dibenzodiazepine derivative possessing a farnesyl residue and isolated from Micromonospora strain [2]. Anthramycin 3 and its analogues, on the other hand, are isolated from Streptomyces strains, possess the tricyclic pyrrole [2,1-c] [1,4]benzodiazepine scaffold and exhibit a unique feature-alkylation of the minor groove of DNA. This feature is caused by appropriate geometry and the presence of binding groups such as an imine, a carbinolamine, or a carbinolamine ether group [3].…”

Section: Introductionmentioning

confidence: 99%

“…During our continuous research on the design and synthesis of novel heterocyclic scaffolds and molecules for application in medicinal chemistry-including furo [2,3-d]pyrimidin-2(3H)-one, 3H-pyrrolo [2,3-d]pyrimidin-2(7H)-one, and 5,6-dihydropyrimido [4,5-c]pyridazin-7(8H)-one analogues [4,5], as well as oxazolo [3,2-f ]pyrimidine-5,7-dione derivatives [6]-we designed and developed a novel synthesis method, leading to the fused tricyclic 1,2,3,4-tetrahydrobenzo[e]pyrazino [1,2-a] [1,4]diazepine-6,12(11H, 12aH)-dione 4. This new, liquid-phase approach is complementary to our previously published, solid-phase synthesis of peptide mimetics, but it surpasses the old method in terms of higher yields and process upscaling capabilities [7].…”

Section: Introductionmentioning

confidence: 99%

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(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione—Synthesis and Crystallographic Studies

Mieczkowski

Trzybiński

Wilczek

et al. 2017

Molbank

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(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H, 12aH)-dione was obtained in a three-step, one-pot synthesis, starting from optically pure (S)-2-piperazine carboxylic acid dihydrochloride. Selective acylation of the β-nitrogen atom followed by condensation with isatoic anhydride and cyclization with HATU/DIPEA to a seven-member benzodiazepine ring, led to the tricyclic benzodiazepine derivative. Crystallographic studies and initial biological screening were performed for the title compound.

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Bicyclic cytarabine analogues: synthesis and investigation of antitumor properties of novel, 6-aryl- and 6-alkyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one arabinosides

Cited by 8 publications

References 34 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

Synthesis Strategies and Biological Value of Pyrrole and Pyrrolopyrimidine

(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione—Synthesis and Crystallographic Studies

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