Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study
Beata Tylińska , Benita Wiatrak , Żaneta Czyżnikowska , Aneta Cieśla-Niechwiadowicz , Elżbieta Gębarowska , Anna Janicka-Kłos
AbstractIn 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.
|Journal series||International Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)|
|Publication size in sheets||0.8|
|Keywords in English||pyrimidine; anticancer; 3,4-dihydronaphthalen; 6-hydrazinopyrimidine; lipophilicity; QSAR study; topoisomerase II; DNA intercalating|
|ASJC Classification||; ; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 140.0, 20-04-2021, ArticleFromJournal|
|Publication indicators||: 2018 = 1.224; : 2018 = 4.183 (2) - 2018=4.331 (5)|
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