A novel class of small molecule inhibitors with radioprotective properties
Language English Country France Media print-electronic
Document type Journal Article
PubMed
31901334
DOI
10.1016/j.ejmech.2019.111606
PII: S0223-5234(19)30740-8
Knihovny.cz E-resources
- Keywords
- 1-(2-hydroxyethyl)piperazine derivative, In vitro, Ionizing radiation, Mice, Radioprotection, Synthesis,
- MeSH
- Apoptosis drug effects MeSH
- Small Molecule Libraries chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Molecular Structure MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Propanols chemical synthesis chemistry pharmacology MeSH
- Radiation-Protective Agents chemical synthesis chemistry pharmacology MeSH
- Molecular Docking Simulation MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Small Molecule Libraries MeSH
- Propanols MeSH
- Radiation-Protective Agents MeSH
The goal of this study was to develop novel radioprotective agents targeting the intrinsic apoptotic pathway and thus decreasing the radiation-induced damage. For that purpose, we designed, synthesized and analyzed ten new compounds based on the 1-(4-(2-hydroxyethyl)piperazin-1-yl)-3-phenoxypropan-2-ol leading structure. The cytotoxicity of the newly synthesized substances was tested in vitro on cell lines derived from different progenitor cells by WST-1 proliferation assay. MTT test was utilized to assess half-maximal inhibitory concentrations and maximum tolerated concentrations of novel compounds in A-549 cells. Screening for radioprotective properties was performed using flow-cytometry in MOLT-4 cells exposed to 60Co ionizing gamma radiation. Selected candidates underwent in vivo testing in C57Bl/6 J mice having a positive impact on their immunological status. In summary, we report here promising compounds with radioprotective effect in vivo.
References provided by Crossref.org
Second-generation piperazine derivatives as promising radiation countermeasures
Substituted Piperazines as Novel Potential Radioprotective Agents
