Discovery of a cinnamyl piperidine derivative as new neddylation inhibitor for gastric cancer treatment
| Autor: | Bo Wang, Xiao-Bing Chen, Hong-Min Liu, Xiao-Jing Li, Sai-Qi Wang, Bin Yu, Qiu-Hua Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Antineoplastic Agents
Apoptosis chemistry.chemical_compound Structure-Activity Relationship Piperidines Stomach Neoplasms Drug Discovery Tumor Cells Cultured Humans Cell Proliferation Pharmacology biology Dose-Response Relationship Drug Molecular Structure Organic Chemistry Piperidine derivative General Medicine Cullin Proteins Cancer treatment chemistry Cinnamates Cancer cell Toxicity biology.protein Cancer research Piperidine Neddylation Drug Screening Assays Antitumor Cullin |
| Zdroj: | European journal of medicinal chemistry. 226 |
| ISSN: | 1768-3254 |
| Popis: | Targeting neddylation pathway has been recognized as an attractive anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is highly desirable. Our work reported the discovery of novel cinnamyl piperidine compounds and their antitumor activity in vitro and in vivo. Among these compounds, compound 4g was identified as a novel neddylation inhibitor and decreased the neddylation levels of cullin 1, cullin 3 and cullin 5. Mechanistic studies demonstrated that compound 4g could inhibit the migration ability of gastric cancer cells and induce apoptosis partly mediated by the Nrf2-Keap1 pathway. Furthermore, in vivo anti-tumor studies showed that 4g effectively inhibited tumor growth without obvious toxicity. Collectively, the cinnamyl piperidine derivatives could serve as new lead compounds for developing highly effective neddylation inhibitors for gastric cancer therapy. |
| Databáze: | OpenAIRE |
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