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

Min Zhong; Ying Lu; Shaolei Li; Xiaolong Li; Zhenming Liu; Xianran He; Yongmin Zhang

doi:10.1016/j.ejmech.2023.115662

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. Epub 2023 Jul 18.

Authors

Min Zhong¹, Ying Lu², Shaolei Li³, Xiaolong Li³, Zhenming Liu⁴, Xianran He⁵, Yongmin Zhang⁶

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: hexianran@163.com.
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: yongmin.zhang@upmc.fr.

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.

MeSH terms

Adenocarcinoma*
Anti-Inflammatory Agents, Non-Steroidal* / chemistry
Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
Antineoplastic Agents* / chemistry
Antioxidants / pharmacology
Cell Line, Tumor
Cell Proliferation
Colonic Neoplasms
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Antioxidants
Anti-Inflammatory Agents, Non-Steroidal