期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 218, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2021.113384
关键词
Selenium; Selenocyanates; Trifluoromethyl selenides; Anticancer; In silico calculations
资金
- National Natural Science Foundation of China [21302065]
- Shenzhen Fushan Biological Technology Co., Ltd.
- China
Twenty new organoselenium compounds were synthesized based on the combination of NSAIDs skeleton and organoselenium motif, showing significant anticancer activity against four types of cancer cell lines. The most active compound exhibited IC50 values lower than 5 mu M, particularly against BGC-823 and MCF-7 cells. Molecular docking study suggested an interaction with thioredoxin reductase 1 as a mechanism for their anticancer activity.
Herein we reported the synthesis of twenty new organoselenium compounds (2a-2j and 3a-3j) based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) skeleton and organoselenium motif (-SeCN and -SeCF3), the anticancer activity was evaluated against four types of cancer cell lines, Caco-2 (human colon adenocarcinoma cells), BGC-823 (human gastric cancer cells), MCF-7 (human breast adenocarcinoma cells), PC-3 (human prostatic cancer cells). Interestingly, the introduction of the -SeCN or -SeCF3 moiety in corresponding parent NSAIDs results in the significant effect on cancer cell lines. Moreover, the most active compound 3a showed IC50 values lower than 5 mu M against the four cancer cell lines, particularly to BGC-823 and MCF-7 with IC50 values of 2.5 and 2.7 mu M, respectively. Furthermore, three compounds 3a, 3g and 3i were selected to investigate their ability to induce apoptosis in BGC-823 cells via modulating the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-8 protein. The redox properties of the NSAIDs-Se derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, molecular docking study revealed that an interaction with the active site of thioredoxin reductase 1 (TrxR1) and predicted the anticancer activity of the synthesized candidates. Overall, these results could serve a promising launch point for further design of NSAIDs-Se derivatives as potential anticancer agents. (c) 2021 Elsevier Masson SAS. All rights reserved.
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