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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506420/ https://www.ncbi.nlm.nih.gov/pubmed/36142688 http://dx.doi.org/10.3390/ijms231810759 |
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author | 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. |
author_facet | 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. |
author_sort | Shmakov, Stanislav V. |
collection | PubMed |
description | 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-9506420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95064202022-09-24 Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents 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. Int J Mol Sci Article 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 IC(50) 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. MDPI 2022-09-15 /pmc/articles/PMC9506420/ /pubmed/36142688 http://dx.doi.org/10.3390/ijms231810759 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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. Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title | Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title_full | Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title_fullStr | Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title_full_unstemmed | Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title_short | Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5′-Pyrimidines] as Potential Antitumor Agents |
title_sort | biological evaluation of 3-azaspiro[bicyclo[3.1.0]hexane-2,5′-pyrimidines] as potential antitumor agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506420/ https://www.ncbi.nlm.nih.gov/pubmed/36142688 http://dx.doi.org/10.3390/ijms231810759 |
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