Discovery of anthraquinone-triazene derivatives as novel antitumor agents causing DNA damage

In this study, 40 anthraquinone-triazene derivatives were designed, and AT-9 and AT-10 were screened out as potential antitumor candidates based on their strong binding affinities to DNA and topoisomerase II using molecular docking and molecular dynamics simulations. Antiproliferative assays revealed that AT-9 and AT-10 exhibited significantly stronger inhibitory effects on A549 and HeLa cell lines compared to the reference mitoxantrone. The binding modes of AT-9 and AT-10 with DNA were confirmed by spectra and gel electrophoresis. Metabolic pathway investigations showed that AT-9 and AT-10 were susceptible to nucleophilic attack by water molecules, leading to the release of nitrogen and degradation into an anthraquinone-amide compound. Thus, the synergistic antitumor mechanism arises from the DNA intercalation of the anthraquinone ring and the alkylating effect mediated by the triazene moiety. Furthermore, ADME analysis revealed that AT-9 and AT-10 possessed favorable drug-likeness and pharmacokinetic properties, indicating strong potential for further development.