{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:39:38Z","timestamp":1783971578810,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund of Bulgaria","award":["KP-06-COST\/10\/2020"],"award-info":[{"award-number":["KP-06-COST\/10\/2020"]}]},{"name":"National Science Fund of Bulgaria","award":["KP-06-H58\/6-19.11.2021"],"award-info":[{"award-number":["KP-06-H58\/6-19.11.2021"]}]},{"name":"National Science Fund of Bulgaria","award":["D01-178\/2022"],"award-info":[{"award-number":["D01-178\/2022"]}]},{"name":"National Science Fund of Bulgaria","award":["D01-183\/2022"],"award-info":[{"award-number":["D01-183\/2022"]}]},{"name":"Bulgarian Ministry of Education and Science","award":["KP-06-COST\/10\/2020"],"award-info":[{"award-number":["KP-06-COST\/10\/2020"]}]},{"name":"Bulgarian Ministry of Education and Science","award":["KP-06-H58\/6-19.11.2021"],"award-info":[{"award-number":["KP-06-H58\/6-19.11.2021"]}]},{"name":"Bulgarian Ministry of Education and Science","award":["D01-178\/2022"],"award-info":[{"award-number":["D01-178\/2022"]}]},{"name":"Bulgarian Ministry of Education and Science","award":["D01-183\/2022"],"award-info":[{"award-number":["D01-183\/2022"]}]},{"name":"National Center for Biomedical Photonics","award":["KP-06-COST\/10\/2020"],"award-info":[{"award-number":["KP-06-COST\/10\/2020"]}]},{"name":"National Center for Biomedical Photonics","award":["KP-06-H58\/6-19.11.2021"],"award-info":[{"award-number":["KP-06-H58\/6-19.11.2021"]}]},{"name":"National Center for Biomedical Photonics","award":["D01-178\/2022"],"award-info":[{"award-number":["D01-178\/2022"]}]},{"name":"National Center for Biomedical Photonics","award":["D01-183\/2022"],"award-info":[{"award-number":["D01-183\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-d]pyrimidines 2\u20135 were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine 3 with IC50 13.42 \u03bcg\/mL (IC50 0.045 \u03bcM), followed by compound 4 (IC50 28.89 \u03bcg\/mL or IC50 0.11 \u03bcM). The thienopyrimidine 4 revealed higher selectivity to MCF-7 and lower activity (IC50 367 \u03bcg\/mL i.e., 1.4 \u03bcM) than compound 3 with MCF-10A cells. With respect to MDA-MB-231 cells, ester 2 manifested the highest effect with IC50 52.56 \u03bcg\/mL (IC50 0.16 \u03bcM), and 2-ethyl derivative 4 revealed IC50 62.86 \u03bcg\/mL (IC50 0.24 \u03bcM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound\u2019s effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.<\/jats:p>","DOI":"10.3390\/molecules28176347","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:30:52Z","timestamp":1693391452000},"page":"6347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["2-Alkyl-Substituted-4-Amino-Thieno[2,3-d]Pyrimidines: Anti-Proliferative Properties to In Vitro Breast Cancer Models"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-5116","authenticated-orcid":false,"given":"Ivan","family":"Iliev","sequence":"first","affiliation":[{"name":"Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 25, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelia","family":"Mavrova","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemical Technologies, University of Chemical Technology and Metallurgy, S8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-9681","authenticated-orcid":false,"given":"Denitsa","family":"Yancheva","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 9, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Dimov","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemical Technologies, University of Chemical Technology and Metallurgy, S8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galya","family":"Staneva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrina","family":"Nesheva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iana","family":"Tsoneva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-9812","authenticated-orcid":false,"given":"Biliana","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2020). Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and by Region, 2000\u20132019, WHO. 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