Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines
Novel 4-amino-thieno[2,3-d]pyrimidine-6-carboxylates substituted at the second position were prepared by cyclocondensation of 2-amino-3-cyano-thiophene and aryl nitriles in an acidic medium. The design of the target compounds was based on structural optimization. The derivatives thus obtained were t...
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MDPI AG
2022-05-01
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| author | Anelia Mavrova Stephan Dimov Inna Sulikovska Denitsa Yancheva Ivan Iliev Iana Tsoneva Galya Staneva Biliana Nikolova |
| author_facet | Anelia Mavrova Stephan Dimov Inna Sulikovska Denitsa Yancheva Ivan Iliev Iana Tsoneva Galya Staneva Biliana Nikolova |
| author_sort | Anelia Mavrova |
| collection | DOAJ |
| description | Novel 4-amino-thieno[2,3-d]pyrimidine-6-carboxylates substituted at the second position were prepared by cyclocondensation of 2-amino-3-cyano-thiophene and aryl nitriles in an acidic medium. The design of the target compounds was based on structural optimization. The derivatives thus obtained were tested in vitro against human and mouse cell lines. The examination of the compound effects on BLAB 3T3 and MFC-10A cells showed that they are safe, making them suitable for subsequent experiments to establish their antitumor activity. The photoirritancy factor of the compounds was calculated. Using the MTT test, the antiproliferative activity to MCF-10A, MCF-7 and MDA-MB-231 cell lines was estimated. The best antiproliferative effect in respect to the MCF-7 cell line revealed compound 2 with IC<sub>50</sub> 4.3 ± 0.11 µg/mL (0.013 µM). The highest selective index with respect to MCF-7 cells was shown by compound <b>3</b> (SI = 19.3), and to MDA-MB-231 cells by compound <b>2</b> (SI = 3.7). Based on energy analysis, the most stable conformers were selected and optimized by means of density functional theory (DFT). Ligand efficiency, ligand lipophilicity efficiency and the physicochemical parameters of the target 4-amino-thienopyrimidines were determined. The data obtained indicated that the lead compound among the tested substances is compound <b>2</b>. |
| first_indexed | 2024-03-10T03:18:31Z |
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| id | doaj.art-9e492df0cfac45439fee3004da9def18 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:18:31Z |
| publishDate | 2022-05-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9e492df0cfac45439fee3004da9def182023-11-23T12:24:31ZengMDPI AGMolecules1420-30492022-05-012710331410.3390/molecules27103314Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell LinesAnelia Mavrova0Stephan Dimov1Inna Sulikovska2Denitsa Yancheva3Ivan Iliev4Iana Tsoneva5Galya Staneva6Biliana Nikolova7Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaDepartment of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl.25, 1113 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 9, 1113 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl.25, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl.21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl.21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl.21, 1113 Sofia, BulgariaNovel 4-amino-thieno[2,3-d]pyrimidine-6-carboxylates substituted at the second position were prepared by cyclocondensation of 2-amino-3-cyano-thiophene and aryl nitriles in an acidic medium. The design of the target compounds was based on structural optimization. The derivatives thus obtained were tested in vitro against human and mouse cell lines. The examination of the compound effects on BLAB 3T3 and MFC-10A cells showed that they are safe, making them suitable for subsequent experiments to establish their antitumor activity. The photoirritancy factor of the compounds was calculated. Using the MTT test, the antiproliferative activity to MCF-10A, MCF-7 and MDA-MB-231 cell lines was estimated. The best antiproliferative effect in respect to the MCF-7 cell line revealed compound 2 with IC<sub>50</sub> 4.3 ± 0.11 µg/mL (0.013 µM). The highest selective index with respect to MCF-7 cells was shown by compound <b>3</b> (SI = 19.3), and to MDA-MB-231 cells by compound <b>2</b> (SI = 3.7). Based on energy analysis, the most stable conformers were selected and optimized by means of density functional theory (DFT). Ligand efficiency, ligand lipophilicity efficiency and the physicochemical parameters of the target 4-amino-thienopyrimidines were determined. The data obtained indicated that the lead compound among the tested substances is compound <b>2</b>.https://www.mdpi.com/1420-3049/27/10/33144-amino-thienopyrimidinescytotoxicityphototoxicityantiproliferationmolecular structurestructure–activity relationship |
| spellingShingle | Anelia Mavrova Stephan Dimov Inna Sulikovska Denitsa Yancheva Ivan Iliev Iana Tsoneva Galya Staneva Biliana Nikolova Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines Molecules 4-amino-thienopyrimidines cytotoxicity phototoxicity antiproliferation molecular structure structure–activity relationship |
| title | Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines |
| title_full | Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines |
| title_fullStr | Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines |
| title_full_unstemmed | Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines |
| title_short | Design, Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines |
| title_sort | design cytotoxicity and antiproliferative activity of 4 amino 5 methyl thieno 2 3 d pyrimidine 6 carboxylates against mfc 7 and mda mb 231 breast cancer cell lines |
| topic | 4-amino-thienopyrimidines cytotoxicity phototoxicity antiproliferation molecular structure structure–activity relationship |
| url | https://www.mdpi.com/1420-3049/27/10/3314 |
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