ArticleMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents2022
SAR study of niclosamide derivatives in the human glioblastoma U-87 MG cells.
Article in Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology.Cancers · 2024Review
- New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, andACS omega · 2024Article
- SAR study of niclosamide derivatives for neuroprotective function in SH-SY5Y neuroblastoma.Bioorganic & medicinal chemistry letters · 2023Article
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Authors and funding
10 authors.
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Abstract
Glioblastoma is a lethal malignant brain tumor, and the development of efficient chemotherapeutic agents remains an urgent need. Niclosamide, an anthelmintic drug, which has been used to treat tapeworm infections more than 50 years, has recently attracted renewed attention due to its evident anticancer activities. It has been shown that niclosamide induces cytotoxicity in human glioblastoma U-87 MG cells corresponding with increased protein ubiquitination, ER stress, and autophagy. Furthermore, niclosamide showed down regulation of multiple pro-survival signaling pathways including Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and STAT3, which further caused reduction of U87-MG cell viability. However, the molecular mechanisms of niclosimide and its derivatives in cancer are not fully understood. In the present article, 12 niclosamide derivatives were synthesized by the replacement of substituents for the structure-activity relationship (SAR) study of the protein ubiquitination and related signaling pathways. Our approach is to identify which substituents of niclosamide play important roles in inducing cell apoptosis, inhibition of cell growth, and down regulation of cell survival signaling pathways. Our results indicate that phenol OH of niclosamide plays a significant role in the anti-glioblastoma activity, while missing Cl (5- or 2'-Cl) showed almost no such effect. 4'-N
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