{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:54:35Z","timestamp":1783979675474,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["RSF 20-15-00332"],"award-info":[{"award-number":["RSF 20-15-00332"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM 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\u2032-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.<\/jats:p>","DOI":"10.3390\/ijms231810759","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:11:10Z","timestamp":1663279870000},"page":"10759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5\u2032-Pyrimidines] as Potential Antitumor Agents"],"prefix":"10.3390","volume":"23","author":[{"given":"Stanislav V.","family":"Shmakov","sequence":"first","affiliation":[{"name":"Laboratory of Nanobiotechnologies, Saint-Petersburg National Research Academic University of the Russian Academy of Sciences, 194021 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana K.","family":"Latypova","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnologies, Saint-Petersburg National Research Academic University of the Russian Academy of Sciences, 194021 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana V.","family":"Shmakova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Health of the Russian Federation, 194156 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-5211","authenticated-orcid":false,"given":"Artem A.","family":"Rubinshtein","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-9342","authenticated-orcid":false,"given":"Mark V.","family":"Chukin","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei G.","family":"Zhuravskii","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Health of the Russian Federation, 194156 Saint-Petersburg, Russia"},{"name":"Scientific Research Center, Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickolay A.","family":"Knyazev","sequence":"additional","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences, 194064 Saint-Petersburg, Russia"},{"name":"Saint-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological), 197758 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Stepakov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia"},{"name":"Department of Organic Chemistry, Saint Petersburg State Institute of Technology, 190013 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Galagudza","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Health of the Russian Federation, 194156 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-2046","authenticated-orcid":false,"given":"Vitali M.","family":"Boitsov","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnologies, Saint-Petersburg National Research Academic University of the Russian Academy of Sciences, 194021 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3389\/fphar.2018.01300","article-title":"Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium","volume":"9","author":"Falzone","year":"2018","journal-title":"Front. 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