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.

癌症仍然是全球死亡的主要原因。尽管近年来癌症治疗取得了显著进展，化疗仍然是一线治疗方法。根据作用机制的不同，常用的化疗药物可以分为几类，包括拓扑异构酶抑制剂。这里报道了一种新合成的salophen型大环席夫碱配体（5E,19E）-3-溴-12,13-二氢二苯并[e,m]吡啶[2,3-i][1,4]二氧杂[8,11]二氮杂十四环（4）及其金属配合物（5a-5d），它们被证明是具有拓扑异构酶IIβ抑制活性的强效抗肿瘤剂。通过计算机模拟对接研究，阐明了这些化合物与拓扑异构酶IIβ酶（PDB ID: 4G0V）活性位点的结合相互作用。对接模拟结果表明，配体在该酶活性位点表现出最有利的结合，其结合能为-10.3 kcal mol⁻¹。此外，使用MTT法针对HepG2肝癌细胞系进行的体外抗肿瘤研究证实了这些发现，显示该配体表现出最强的抑制作用，IC₅₀值为0.09 μM，与标准抗癌药物多柔比星相当。