A salophen-type macrocyclic Schiff base ligand and its metal complexes: exploring in vitro anticancer efficacy via in silico topoisomerase IIβ enzyme targeting

Abstract

Cancer persists as a principal cause of global mortality. Despite significant progress in cancer therapeutics in recent decades, chemotherapy remains a primary modality for cancer treatment. Based on their mechanism of action, commonly used chemotherapeutic agents can be classified into several categories, including topoisomerase inhibitors. Here, a newly synthesized salophen-type macrocyclic Schiff-base ligand (5E,19E)-3-bromo-12,13-dihydrodibenzo[e,m]pyrido[2,3-i][1,4]dioxa[8,11]diazacyclotetradecine (4) and its metal complexes (5a–5d) have been reported as potent anticancer agents exhibiting topoisomerase IIβ inhibitory activity. In silico docking studies elucidated their binding interactions with the active site of the topoisomerase IIβ enzyme (PDB ID: 4G0V). The docking simulation results indicated that the ligand exhibited its most favorable interaction with a binding energy of −10.3 kcal mol⁻¹. Also, in vitro anticancer studies using the MTT assay against the HepG2 liver cancer cell line corroborated these findings, demonstrating that the ligand exhibited its strongest inhibitory action with an IC₅₀ of 0.09 μM, comparable to that of the standard anticancer drug doxorubicin.