Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2-Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

The present work emphasizes the utility of 2,4-dichloro-5-methylbenzo[h][1,6]naphthyridine as starting precursors. The reaction of 2,4-dichloro-5-methylbenzo[h][1,6]naphthyridine with a variety of aliphatic and aromatic amines yielded 2-amino substituted 2,4-dichlorobenzo[h]naphthyridines. All the compounds were examined for their in vitro anticancer activity against six human cancer lines and docked with PDK1 inhibitors. The structure-activity relationship studies are revealed that the compounds holding aminocarbazole moiety and triazole amine moiety improve the activity profile. All the structures of synthesized compounds were optimized at B3LYP-D3/6-31G(d) level in the water. Furthermore, the electronic properties and biological reactivity of the synthesized compounds are explored using computational techniques.