Abstract
Aim of this research is to construct a library via amide formation under solution-phase condition. To synthesize the core compound：a linker with amino and azido groups at the terminal end of butane, 4-azidobutan-1-amine), was prepared。After coupling with the activated acid derivatives of fenbufen and ethacrynic acid, the azido group was reduced to deliver the primary amines which could serve as a new core amine compound for construction of the library. The cell lines used in our library included A549、MCF7、C26、and Tramp, which were derivated from lung cancer, breast cancer, colon cancer and pancreas cancer, respectively. Through the screening on the basis of the four different types of cancers, potential compound with selectivity may be easily discovered. Indeed, after the first round of screening, three compound with improved cytotoxicity were found, e.g. N-(4-(4-(biphenyl-4-yl)-4- oxobutanamido)butyl)-5-(2,5-dimethylphenoxy)-2,2-dimethylpentanamide、N-(4-(4-(biphenyl-4-yl)-4-oxobutanamido) butyl)-2-ethylhexanamide and 4-(biphenyl-4-yl)-N-(4-(2-(2,3- dichloro-4-(2-methylenebutanoyl)phenoxy)acetamido)butyl)-4-oxobutanamide. Further prepare of these compound and purification to determinate the IC50 value were performed. We can see that one-step synthesis linker to modify potential compound is succeed in our library system. In addition, we primary screening some potential anti-cancer compound seems that may have cytotoxic selectivity. Overall, we find that modified Fenbufen core amine is more cytotoxic than modified EA core amine.