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 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.

Automated summary

New pyrimidine derivatives were designed, synthesized, and analyzed for their anticancer properties in this study. The compounds exhibited inhibitory activity on various cancer cell lines, with stronger impact on P-glycoprotein activity in doxorubicin-resistant cell cultures. These compounds showed more lipophilic character than doxorubicin, determining their affinity for molecular targets and passive transport through biological membranes. Additionally, their potential as inhibitors of topoisomerase II and DNA intercalation was investigated through molecular docking.