School of Chemical Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India.
Cancer Research Program (CRP), Bio-Nano Therapeutics Research Laboratory, School of Life Sciences, Department of Zoology, Bharathiar University, Coimbatore 641 046, India.
Bioorg Chem. 2020 Apr;97:103709. doi: 10.1016/j.bioorg.2020.103709. Epub 2020 Feb 28.
A series of novel 8-nitro quinoline-based thiosemicarbazone analogues were synthesized and characterized by various spectroscopic and single crystal X-ray analyses. The potent antitumor effects of synthesized compounds towards the cancer cells were evaluated by MTT assay. Amongst, the compound 3a exhibited the highest inhibitory activity and the compounds 3f and 3b were also showed significant activity. The molecular mechanistic studies of cell death have demonstrated that the treated potent compound 3a induced G1/S & G2/M phase cell cycle arrest and induced apoptosis via mitochondrial dysfunction and increased the production of cytotoxic ROS levels. The RT-PCR gene expression analysis revealed that the cell death induced by activation of caspase-3 dependent intrinsic apoptotic signaling pathway. Further, the molecular binding affinity of compounds with estrogen receptor alpha was calculated by molecular docking studies. Thus, novel 8-nitro quinoline-thiosemicarbazone analogues provide a unique tool for breast cancer therapeutic tactics.
一系列新型 8-硝基喹啉基缩硫代氨基脲类似物被合成并通过各种光谱和单晶 X 射线分析进行了表征。通过 MTT 测定法评估了合成化合物对癌细胞的抗肿瘤作用。其中，化合物 3a 表现出最高的抑制活性，化合物 3f 和 3b 也表现出显著的活性。细胞死亡的分子机制研究表明，处理强效化合物 3a 通过线粒体功能障碍诱导 G1/S 和 G2/M 期细胞周期阻滞并诱导细胞凋亡，并增加细胞毒性 ROS 水平的产生。RT-PCR 基因表达分析显示，细胞死亡是通过激活 caspase-3 依赖性内在凋亡信号通路诱导的。此外，通过分子对接研究计算了化合物与雌激素受体 α 的分子结合亲和力。因此，新型 8-硝基喹啉-缩硫代氨基脲类似物为乳腺癌治疗策略提供了独特的工具。
