| Lung cancer causes the most cancer deaths in the world today,and breast cancer is the most common malignant tumor among women at present.But drugs used to treat these two kinds of cancer are very limited.Therefore,development of new drugs targeting these two cancers is very necessary.Molecular targeted therapy is a new method for treatment of cancer.Searching for new drug targets and discovery of new small molecule drugs targeting specific genes has become research hotpot.There is a small molecular compound library in our lab,which was bought from Life Chemicals Company and contains 22000 small molecular compounds.These compounds have new and various structure,and were designed according to drug development.In this study,we detected effect of 560 compounds in this library in repressing growth of MCF-7 and A549 cells.Cell viability was analyzed with WST-1 after compounds treatment.The results showed 6 compounds among the 560 compounds could significantly repress both MCF-7 and A549 cell growth and had significant effect of concentration dependence.The compound 3G11 had highest inhibition rate in A549 cell growth,and the inhibition rate was 72.91%when concentration was 10?mol/L.The IC50 of compound 3G11 was 2.407 ?mol/L calculated by GraphPad Prism.The inhibition rate of compound 3G11 in MRC-5 cell growth was significantly lower than that in A549 cell growth.When concentration was 10 ?mol/L,the inhibition rate of compound 3G11 in MRC-5 cell growth was 30.41%.The results of structure-activity relationship analysis showed a plurality of benzene structural integrity and benzene and structure?heterocyclic structure and halogen groups.were important for small molecules in inhibition of cell growth.The compound 3G11 promoted expression of bax and Bcl-xl in A549 cells,which suggested 3G11 may promote apoptosis of A549 cells.These results supplied helpful information for further study of development new small molecule drug using 3G11 as the drug lead compound. |
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