Investigation of the anticancer activity of modified 4-hydroxyquinolone analogues: in vitro and in silico studies.

A set of nitrogen-based heterocycles derived from the quinoline ring as well as cyclohexanedione and dimedone cores were subjected to in vitro anticancer activity evaluation against four different cancerous cell lines namely; HCT116, A549, PC3, and MCF-7 respectively to colon, lung, prostate, and breast cancers. Compound 3g presented promising results exhibiting the best IC(50) values among the investigated compounds for the four tested cell lines. In vitro results were supported with in silico studies including molecular docking simulation in order to learn more about the binding mode of the studied derivatives with relevant drug targets in cancer treatment, namely; anaplastic lymphoma kinase and cyclin-dependent kinase 2. Compound 3g showing the best in vitro results exhibited the most promising docking scores among the studied compounds. Moreover, molecular dynamics simulation was performed to the best ligand studying its stability inside the selected enzymes. Furthermore, a DFT study was performed to investigate the structural composition, electron density, and reactivity of tested compounds to identify the most important parts of the derivatives and elaborate a structure-activity relationship.