No abstract

New series of 18 compounds were synthesized using sorafenib derivatives as parent structure and p‐aminoacetophenone as raw materials. The structures of the newly synthesized compounds were confirmed on the basis of 1H, 13C NMR and HRMS (Supporting Information). Their antitumor activities against human lung adenocarcinoma cells A549 (A549), prostate cancer cells PC‐3 (PC‐3), human chronic myeloid leukemia cells (K562), and human liver cancer cells (HepG2) in vitro were evaluated, using Sorafenib as a positive control drug. Bioactivity assays indicated that these compounds showed good antitumor activities toward tested four cancer cell lines. In particular, compound 7n showed potent inhibitory activity with IC50 of 7.39 ± 1.51 μM toward K562. The mechanism and the apoptosis inducing effect of 7n against k562 cell line were studied. The results showed that compound 7n blocked K562 cells in G2/M phase to induce cell apoptosis with a concentration and time‐dependent manner.

New series of 17 pyrimidinamine derivatives containing urea moiety were designed and synthesized. Their antitumor activity was investigated by MTT method. The results showed that some of these compounds exhibited moderate to good antitumor activities against all four cancer cell lines. The IC50 value of compound HD-6 on PC-3 cells was better 2.37 μM than the positive control drug sorafenib (3.66 μM). The inhibitory activity of most target compounds on HepG2 cells was better than that of positive drug sorafenib (10.70 μM). Among them, the IC50 value of compound HD-6 on K562 cells was 6.80 μM, which close to solafinib (4.62 μM). Further studies revealed that compound HD-6 clearly possessed apoptosis inducing effects, increased the level of reactive oxygen species, arrested the cycle in the G2/M phase and regulated the expression of tyrosine kinase EGFR in PC-3 cells.