Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents

Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents

A series of heterocyclic compounds containing spirofused barbiturate and 3-azabicyclo[3.1.0]hexane frameworks have been studied as potential antitumor agents. Antiproliferative activity of products was screened in human erythroleukemia (K562), T lymphocyte (Jurkat), and cervical carcinoma (HeLa) as...

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Published in:International journal of molecular sciences Vol. 23; no. 18; p. 10759
Main Authors: Shmakov, Stanislav V., Latypova, Diana K., Shmakova, Tatiana V., Rubinshtein, Artem A., Chukin, Mark V., Zhuravskii, Sergei G., Knyazev, Nickolay A., Stepakov, Alexander V., Galagudza, Michael M., Boitsov, Vitali M.
Format: Journal Article
Language:English
Published: Basel MDPI AG 15-09-2022
MDPI
Subjects:
3-azaspiro[bicyclo[3.1.0]hexane-2,5′-pyrimidines]
Actin
alloxan-derived azomethine ylide
Apoptosis
Arthritis
cancer cell lines (K-562
Cancer therapies
Cell cycle
Cell death
Cervical cancer
Cervical carcinoma
Cervix
Colon
Confocal microscopy
cyclopropenes
Cytoplasm
Drug resistance
Erythroleukemia
Filaments
HeLa
Heterocyclic compounds
Hexanes
Jurkat
Lymphocytes
Lymphocytes T
Motility
Natural products
Pyrimidines
Tumors
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Summary:A series of heterocyclic compounds containing spirofused barbiturate and 3-azabicyclo[3.1.0]hexane frameworks have been studied as potential antitumor agents. Antiproliferative activity of products was screened in human erythroleukemia (K562), T lymphocyte (Jurkat), and cervical carcinoma (HeLa) as well as mouse colon carcinoma (CT26) and African green monkey kidney epithelial (Vero) cell lines. The most effective among the screened compounds show IC50 in the range from 4.2 to 24.1 μM for all tested cell lines. The screened compounds have demonstrated a significant effect of the distribution of HeLa and CT26 cells across the cell cycle stage, with accumulation of cells in SubG1 phase and induced apoptosis. It was found, using a confocal microscopy, that actin filaments disappeared and granular actin was distributed diffusely in the cytoplasm of up to 90% of HeLa cells and up to 64% of CT26 cells after treatment with tested 3-azaspiro[bicyclo [3.1.0]hexane-2,5′-pyrimidines]. We discovered that the number of HeLa cells with filopodium-like membrane protrusions was reduced significantly (from 91% in control cells to 35%) after treatment with the most active compounds. A decrease in cell motility was also noticed. Preliminary in vivo experiments on the impact of the studied compounds on the dynamics of CT26 tumor growth in Balb/C mice were also performed.
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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810759