新型 NSAIDs-EBS 衍生物的合成、细胞毒性、抗氧化活性及分子模拟。
Synthesis, cytotoxicity, antioxidant activity and molecular modeling of new NSAIDs-EBS derivatives.
机构信息
Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China; Key Laboratory of Optoelectronic Chemical Materials and Devices, Jianghan University, Wuhan, 430056, China.
Key Laboratory of Optoelectronic Chemical Materials and Devices, Jianghan University, Wuhan, 430056, China.
出版信息
Eur J Med Chem. 2023 Nov 5;259:115662. doi: 10.1016/j.ejmech.2023.115662. Epub 2023 Jul 18.
Two series of NSAIDs-EBS derivatives (5a-j and 9a-i) based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and Ebselen moiety were synthesized. Their cytotoxicity was evaluated against five types of human cancer cell lines, BGC-823 (human gastric cancer cell line), SW480 (human colon adenocarcinoma cells), MCF-7 (human breast adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells). Moreover, the most active compound 5j showed IC values below 3 μM in all cancer cell lines and with remarkable anticancer activity against MCF-7 (1.5 μM) and HeLa (1.7 μM). The redox properties of the NSAIDs-EBS derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, TrxR1 inhibition activity assay and molecular docking study revealed NSAIDs-EBS derivatives could serve as potential TrxR1 inhibitor.
基于非甾体抗炎药（NSAIDs）骨架和 Ebselen 部分的杂交，我们合成了两系列 NSAIDs-EBS 衍生物（5a-j 和 9a-i）。评估了它们对五种类型的人类癌细胞系（BGC-823（人胃癌细胞系）、SW480（人结肠腺癌细胞）、MCF-7（人乳腺癌细胞系）、HeLa（人宫颈癌细胞系）、A549（人肺癌细胞系））的细胞毒性。此外，最活跃的化合物 5j 在所有癌细胞系中的 IC 值均低于 3 μM，对 MCF-7（1.5 μM）和 HeLa（1.7 μM）具有显著的抗癌活性。通过 2,2-二苯基-1-苦基肼（DPPH）、博来霉素依赖性 DNA 损伤和谷胱甘肽过氧化物酶（GPx）样测定研究了所制备的 NSAIDs-EBS 衍生物的氧化还原性质。最后，TrxR1 抑制活性测定和分子对接研究表明，NSAIDs-EBS 衍生物可以作为潜在的 TrxR1 抑制剂。
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