The 8-Hydroxyquinoline Derivatives of 1,4-Naphthoquinone: Synthesis, Computational Analysis, and Anticancer Activity

Anticancer drug design has been reformed by the creation of heterocyclic hybrids. The introduction of a quinoline scaffold affects the activity, toxicity, and bioavailability of new compounds. The aim of this study was to synthesize and evaluate the biological activity of hybrids of 1,4-naphthoquinone with the 8-hydroxyquinoline moiety. The structure of the new compounds was characterized using spectroscopic methods, such as HR-MS, NMR, and IR. The analysis was supplemented by calculated NMR and IR spectra. The physicochemical properties and bioavailability of the compounds were examined using in silico methods. An analysis of reactivity descriptors showed that the compounds are good electron acceptors and exhibit high reactivity. Bioavailability properties confirm that hybrids could be good oral administration drugs. The biological potential of hybrids was examined by designation of the enzymatic conversion rate of the NQO1 protein and in vitro against cancer cell lines with overexpression of the gene encoding the NQO1 protein. The possibility of interaction between the tested ligand and the NQO1 protein was examined by molecular docking methods.