Preliminary Study Of The Anti-tumor Role Of YN33Series Compounds

Objective：To screen8series of YN33compounds, which are EGFRtyrosine kinase inhibitors, and evaluate their anti-tumor effect in vitro.Method:(1) Preliminary screening was carried out by detecting theEGFR kinase phosphorylation inhibition activity of the compounds.（2）MTS assay was adopted for secondary anti-tumor screen of the selectedcompounds using A431,N87and BT474cell lines in vitro.(3) Toinvestigate the influence caused by the sreened compound YN33-5innormal cells, MTS assay was carried out in MRC-5cell line as well.(4)Theeffect of YN33-5on cell cycle by flow cytometry analysis.Results:(1) According to the kinase assay,4compouds were selected,which were YN33-3, YN33-5, YN33-6, and YN33-8. YN33-5and YN33-8showed significant inhibitive.(2)After furth screening in vitro,YN33-5showed significant growth inhibitive effect on A431,BT474and N87,IC50respectively:（9.7433±2.7959）μmol/L,（4.6117±2.2225）nmol/L and（44.0483±21.7931） nmol/L, and the inhibition effect weredose-dependent.(3)In cell lines of the MRC-5proliferation inhibitexperiment that,YN33-5damage slightly higher than lapatinib.(4)In the furth study,YN33-5had obvious inhibitive effects on the proliferation ofA431,BT474and N87cells in dose-dependent and time-dependentmanner.The results of flow cytometry analysis demonstrated that YN33-5were observed to block A431,BT474and N87cells in G1phase of cellcycle.Conclusion:YN33-5which were identified by screening in vitroexhibited potent antitumor activity.It inhibited the proliferation ofA431,BT474and N87tumor cell lines in dose-dependent manner whilediffered inhibition degree. YN33-5is probably an effective EGFR tyrosinekinase inhibitor.