在此，通过考虑已知 DNA 嵌入剂和拓扑异构酶 II 抑制剂的药效团特征，合成了一系列靛红束缚的吲哚并[2,3-b]喹喔啉杂合体。针对卵巢癌细胞系（SKOV-3 和 Hey A8）评估了合成化合物的抗增殖特性。其中四种化合物表现出有希望的抗增殖活性，其中一种对耐药性 Hey A8 细胞的作用比顺铂强 10 倍。进行了进一步的研究以确定最活跃的化合物的 DNA 嵌入亲和力作为其抗增殖活性的潜在机制。进行 ADMET 计算机研究以评估活性化合物的物理化学、药代动力学和毒性参数。据我们所知，这项研究是第一份关于靛红-吲哚喹喔啉杂合体作为开发新型 DNA 嵌入剂的结构蓝图潜力的报告。此外，它还探索了它们在卵巢癌中规避铂类耐药性的潜力。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.Copyright © 2023 Elsevier Inc. All rights reserved.