Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study
In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According t...
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/3825 |
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| author | Beata Tylińska Benita Wiatrak Żaneta Czyżnikowska Aneta Cieśla-Niechwiadowicz Elżbieta Gębarowska Anna Janicka-Kłos |
| author_facet | Beata Tylińska Benita Wiatrak Żaneta Czyżnikowska Aneta Cieśla-Niechwiadowicz Elżbieta Gębarowska Anna Janicka-Kłos |
| author_sort | Beata Tylińska |
| collection | DOAJ |
| description | In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking. |
| first_indexed | 2024-03-10T12:32:51Z |
| format | Article |
| id | doaj.art-67333f164a9d475fa3bf256ffff5fa89 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:32:51Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-67333f164a9d475fa3bf256ffff5fa892023-11-21T14:31:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228382510.3390/ijms22083825Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking StudyBeata Tylińska0Benita Wiatrak1Żaneta Czyżnikowska2Aneta Cieśla-Niechwiadowicz3Elżbieta Gębarowska4Anna Janicka-Kłos5Department of Organic Chemistry, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Polandepartment of Pharmacology, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wrocław, PolandDepartment of Inorganic Chemistry, Wroclaw Medical University, Borowska 211A, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Basic Medical Sciences, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandAgricultural Microbiology Lab, Department of Plant Protection, Wrocław University of Environmental and Life Sciences, Grunwaldzka 53, 50-375 Wrocław, PolandDepartment of Inorganic Chemistry, Wroclaw Medical University, Borowska 211A, Borowska 211A, 50-556 Wroclaw, PolandIn the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.https://www.mdpi.com/1422-0067/22/8/3825pyrimidineanticancer3,4-dihydronaphthalen6-hydrazinopyrimidinelipophilicityQSAR study |
| spellingShingle | Beata Tylińska Benita Wiatrak Żaneta Czyżnikowska Aneta Cieśla-Niechwiadowicz Elżbieta Gębarowska Anna Janicka-Kłos Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study International Journal of Molecular Sciences pyrimidine anticancer 3,4-dihydronaphthalen 6-hydrazinopyrimidine lipophilicity QSAR study |
| title | Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study |
| title_full | Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study |
| title_fullStr | Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study |
| title_full_unstemmed | Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study |
| title_short | Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study |
| title_sort | novel pyrimidine derivatives as potential anticancer agents synthesis biological evaluation and molecular docking study |
| topic | pyrimidine anticancer 3,4-dihydronaphthalen 6-hydrazinopyrimidine lipophilicity QSAR study |
| url | https://www.mdpi.com/1422-0067/22/8/3825 |
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