Synthesis and Anti-tumor Activity of Novel Quinazolin-4-one Derivatives

A series of novel C-2 and N-3 disubstituted quinazolin-4(3H)-one derivatives 5 possessing amino acid chain were synthesized by the addition reaction of imine with iminoketene and aromatization using anthranilic acid, aromatic aldehyde and glycine ethyl ester as starting materials. After elimination of carboxymethyl in the acidic condition, novel quinazolin-4( 3H)-one derivatives 9 bearing amino side chain were designed and synthesized by SN2 substitution reaction. The compounds were evaluated for their anti-proliferation activities against four tumor cells. The results showed that some of the compounds, such as 9ba and 9bc showed significantly anti Hela activity with the IC50 values of 8.16 mu M and 7.47 mu M, respectively, while 9bc and 9bd against A549 with the IC50 values of 5.62 mu M and 9.54 mu M, respectively. Structure activity relationship analysis of these analogues suggested that coumarin substituent (extended pi planar aromatic ring) on C-2 position and the introduction of amino side chain should be favorable to their anti-tumor activities.