选择性地启动程序性细胞死亡在癌细胞中而非正常细胞中的反应是一种有吸引力的化疗策略。在本研究中，合成了一系列具有反应性氧自由基（ROS）调节功能基团的合成二香豆素衍生物，并利用MTT实验检测它们在四种癌细胞系和两种正常细胞系中的细胞毒性活性。在这些化合物中，3 l被发现是在各种癌细胞系中诱导人肾癌细胞（SKRC-45）凋亡最有前途的衍生物。与顺铂相比，3 l对正常肾细胞的细胞毒性显著较低。该化合物通过调节p53介导的凋亡途径产生ROS，降低线粒体膜电位和引起DNA断裂，能够诱导凋亡和细胞周期阻滞。与顺铂不同，3 l衍生物被发现能够抑制SKRC-45细胞中NF-κB的核定位。它还通过下调COX-2/ PTGES2级联和MMP-2减少SKRC-45细胞的增殖、存活和迁移能力。在体内肿瘤模型中，3 l显示出抗癌效应，通过减少平均肿瘤质量、体积并诱导caspase-3激活，同时不影响肾功能。进一步的研究需要确立3 l作为有前途的抗癌药物候选剂。版权所有 © 2023 Elsevier Inc.发布。

Selective initiation of programmed cell death in cancer cells than normal cells is reflected as an attractive chemotherapeutic strategy. In the current study, a series of synthetic bis-coumarin derivatives were synthesized possessing reactive oxygen species (ROS) modulating functional groups and examined in four cancerous and two normal cell lines for their cytotoxic ability using MTT assay. Among these compounds, 3 l emerged as the most promising derivative in persuading apoptosis in human renal carcinoma cells (SKRC-45) among diverse cancer cell lines. 3 l causes significantly less cytotoxicity to normal kidney cells compared to cisplatin. This compound was able to induce apoptosis and cell-cycle arrest by modulating the p53 mediated apoptotic pathways via the generation of ROS, decreasing mitochondrial membrane potential, and causing DNA fragmentation. Unlike cisplatin, the 3 l derivative was found to inhibit the nuclear localisation of NF-κB in SKRC-45 cells. It was also found to reduce the proliferation, survival and migration ability of SKRC-45 cells by downregulating COX-2/ PTGES2 cascade and MMP-2. In an in vivo tumor model, 3 l showed an anticancer effect by reducing the mean tumor mass, volume and inducing caspase-3 activation, without affecting kidney function. Further studies are needed to establish 3 l as a promising anti-cancer drug candidate.Copyright © 2023. Published by Elsevier Inc.