Amide-based derivatives of acridine display multifaceted anticancer targeting: An in silico-based mechanistic study

Context: The ongoing challenges with chemotherapy demand continuous efforts to discover new drug molecules. In this scenario, a multi-target approach could be of special advantage. This might not only decrease the likelihood of drug resistance but also ensure a broader spectrum and a multifaceted, convergent attack on tumor cells. In this context, anthracene-based compounds are of key interest. Aims: To explore the activity and hybrid nature of acridine-based derivatives. Methods: In silico approach was applied, and the compounds were tested against seven different protein targets playing significant roles in cancer pathogenesis. Results: Based on the binding affinities of the compounds, it was found that, in addition to being excellent intercalating agents, the compounds displayed high inhibition for several protein targets, most importantly tyrosine kinases. Specifically, the ligands with imidazole and hydroxyethyl amino groups were found to be potent against all targets except for EGFR and ROS. The docking scores of the tested compounds were higher than those of the standard drugs in many instances. In silico ADME prediction showed that all compounds fell within the prescribed ranges, thus making them ideal candidates for oral delivery. Conclusions: The proposed compounds not only demonstrated strong anticancer activity but also exhibited their activity through multiple pathways, thereby overcoming several therapeutic challenges currently faced.