Synthesis, cytotoxicity, antioxidant activity and molecular modeling of new NSAIDs-EBS derivatives

  • Eur J Med Chem. 2023 Nov 5;259:115662. doi: 10.1016/j.ejmech.2023.115662.
Min Zhong  1 ,  Ying Lu  2 ,  Shaolei Li  3 ,  Xiaolong Li  3 ,  Zhenming Liu  4 ,  Xianran He  5 ,  Yongmin Zhang  6
Affiliations
  • 1. 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.
  • 2. Key Laboratory of Optoelectronic Chemical Materials and Devices, Jianghan University, Wuhan, 430056, China.
  • 3. Shenzhen Fushan Biological Technology Co., Ltd, Kexing Science Park A1 1005, Nanshan Zone, Shenzhen, 518057, China.
  • 4. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
  • 5. Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China. Electronic address: [email protected].
  • 6. Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China; Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, 571158, China. Electronic address: [email protected].
PMID: 37482018 DOI: 10.1016/j.ejmech.2023.115662
Abstract

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 IC50 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.

Keywords
Anticancer; Ebselen; Molecular modeling; NSAIDs; Selenium.
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