Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Molecules. 2021 Feb 3;26(4):786. doi: 10.3390/molecules26040786.
Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound was the most potent against MDA-MB-231 cells, with IC value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound could be promising lead compound for further antitumor drug research.
香豆素具有不可估量的抗肿瘤潜力，且副作用极小，这取决于基本核上的取代基，为抗肿瘤药物的开发展示了广阔的前景。为了开发新型抗肿瘤候选药物，设计并合成了一系列香豆素磺酰胺和酰胺衍生物。这些衍生物中的大多数对 MDA-MB-231 和 KB 细胞系表现出良好的细胞毒性活性，其中化合物 对 MDA-MB-231 细胞的活性最强，IC 值为 9.33 μM，与 5-氟尿嘧啶相当。进一步的研究表明，化合物 对肿瘤具有多种作用，包括抑制细胞迁移和侵袭以及诱导细胞凋亡。活性氧（ROS）测定和 Western blot 分析表明，化合物 通过增加 ROS 水平并上调 MDA-MB-231 细胞中 caspase-3 的表达来促进癌细胞凋亡。这些结果表明，化合物 可能是进一步抗肿瘤药物研究有前途的先导化合物。
