Rational design, synthesis, pharmacophore modeling, and docking studies for identification of novel potent DNA-PK inhibitors.

摘要: Abstract Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward repair pathways. Hence, the search potent and selective inhibitors particularly considered state-of-the art several series have been designed. In this article, a novel benchmark database 43 compounds was built described. Ligand-based approaches including pharmacophore QSAR modeling were applied models introduced analyzed predicting activity test candidates. Based results, we gave report synthesis fifteen 2-((8-methyl-2-morpholino-4-oxo-4 H -benzo[ e ][1,3]oxazin-7-yl)oxy)acetamide derivatives vitro evaluation inhibitory antiproliferative activities. These overall are satisfied with Lipinski's rule five. The biological testing showed five promising active 7c , 7d 7f 9e 9f micromolar range from 0.25 to 5 µM. addition, SAR investigated confirmed that terminal aryl moiety found be quite crucial activity. Moreover flexible docking simulation done into putative binding site 3D homology model probable interaction between ligands interpreted.