Yadav Monika, Yadav Deepak, Singh Dharam Pal, Kapoor Jitander Kumar
Department of Chemistry, National Institute of Technology Kurukshetra-136119, Haryana, India.
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh-160012, India.
Dalton Trans. 2025 Jul 1;54(26):10358-10369. doi: 10.1039/d5dt00993f.
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 (5,19)-3-bromo-12,13-dihydrodibenzo[,]pyrido[2,3-][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. 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. Also, 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 IC 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。尽管近几十年来癌症治疗取得了重大进展，但化疗仍然是癌症治疗的主要方式。根据其作用机制，常用的化疗药物可分为几类，包括拓扑异构酶抑制剂。在此，一种新合成的萨罗芬型大环席夫碱配体（5,19）-3-溴-12,13-二氢二苯并[,]吡啶并[2,3-][1,4]二氧杂[8,11]二氮杂环十四烷（4）及其金属配合物（5a-5d）已被报道为具有拓扑异构酶IIβ抑制活性的强效抗癌剂。对接研究阐明了它们与拓扑异构酶IIβ酶活性位点（PDB ID：4G0V）的结合相互作用。对接模拟结果表明，该配体表现出最有利的相互作用，结合能为-10.3 kcal mol。此外，使用MTT法对HepG2肝癌细胞系进行的抗癌研究证实了这些发现，表明该配体表现出最强的抑制作用，IC为0.09 μM，与标准抗癌药物阿霉素相当。
