New spiro-linked indolinone pyrrolidine selenoxoimidazolones

Novotortsev, Vladimir K.; Kukushkin, Maxim E.; Тафеенко, В. А.; Зык, Н. В.; Белоглазкина, Е. К.

doi:10.1016/j.mencom.2020.05.020

Cited by 9 publications

(5 citation statements)

References 10 publications

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“…For compounds 4a-m , the 1 H and 13 C NMR spectra contain a single set of signals; the Z-configuration was assigned to products based on the literature analogies [ 4 ]. The Z configuration of compound 4b was also indirectly confirmed by the X-ray diffraction data for the product of its reaction with azomethine ylide (compound 6b [ 36 ]).…”

Section: Resultsmentioning

confidence: 96%

“…For dispiroindolinones 6 , the 1 H NMR spectrum was characteristically in the range of 3.50–2.90 ppm, in which there were four doublets with J~10 Hz corresponding to the protons of the pyrrolidine fragments (see Supplementary Information ). The (5R*, 4′R*) configuration of compound 6b was proven by the X-ray diffraction data [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

“…The structural types of the synthesized compounds are shown in Figure 1 . The synthesis of the type 1 compounds are firstly described here; compounds of type 2 were recently presented by us in a short communication of a single example (R 1 = 4-EtO-C 6 H 4 ) [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability

Novotortsev

Kukushkin

Тафеенко

et al. 2021

IJMS

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A regio- and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoimidazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system—namely, 2-selenoxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3″-indoline]-2″,5-diones (6a-m)—were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6–8.7 μM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2–6.9 and compound 6e—against the MCF7 cancer cell line (CC50 20.6 μM, HEK293T/A549 selectivity index 1.6); some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

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Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability

Novotortsev

Kukushkin

Тафеенко

et al. 2021

IJMS

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“…Selenohydantoin derivatives 6g, 6h, 6q, 6r may be readily obtained from sarcosine, paraformaldehyde and the corresponding indolidene-selenohydantoins5g, 5h, 5q, 5r according to the modified method described in [26,34] (Scheme 3). .…”

Section: Chemistrymentioning

confidence: 99%

“…. Selenohydantoin derivatives 6g, 6h, 6q, 6r may be readily obtained from sarcosine, paraformaldehyde and the corresponding indolidene-selenohydantoins 5g, 5h, 5q, 5r according to the modified method described in [26,34] (Scheme 3). O-containing derivatives 9 were synthesized from S-alkylated derivatives 7 of corresponding thiohydantoins 3 (Scheme 4).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles

et al. 2021

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A series of novel S-, O- and Se-containing dispirooxindole derivatives has been synthesized using 1,3-dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5-indolidene-2-chalcogen-imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53+/+ over HCT116 p53−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell-based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range.

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Synthesis of 4,4′-substituted 2,2′-[ethane-1,2-diylbis(selanediyl)]bis(1H-imidazol-5(4H)-ones)

et al. 2021

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New spiro-linked indolinone pyrrolidine selenoxoimidazolones

Cited by 9 publications

References 10 publications

Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability

Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability

Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles

Synthesis of 4,4′-substituted 2,2′-[ethane-1,2-diylbis(selanediyl)]bis(1H-imidazol-5(4H)-ones)

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