Design, synthesis, crystal structures and anticancer activity of 4-substituted quinolines to target PDK1

The induced fit docking of anilino quinoline scaffold results in the required hydrogen bonding interactions with amino acid residues in the orthosteric site of 3 Phosphoinositide dependent kinase (PDK1). The rational design of 4-substituted amino quinolines is carried out and eight compounds are synthesized. Four crystal structures are determined and their binding mode with adenosine triphosphate (ATP) site of PDK1 is analyzed. The anticancer activity in A549 cell lines of the test compounds by MTT assay resulted in an inhibitor with IC50 value of 0.96 mu M which is less than the pemetrexed, a marketed lung cancer drug.