Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33550073
DOI
10.1016/j.bioorg.2021.104660
PII: S0045-2068(21)00036-5
Knihovny.cz E-resources
- Keywords
- Antiproliferative, DNA binding, G-quadruplexes, Perylenemonoimide,
- MeSH
- G-Quadruplexes drug effects MeSH
- Imides chemical synthesis chemistry pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mitochondria drug effects MeSH
- Molecular Structure MeSH
- Perylene analogs & derivatives chemical synthesis chemistry pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Imides MeSH
- Perylene MeSH
- perylenemonoimide MeSH Browser
A structure-activity relationship (SAR) study in terms of G-quadruplex binding ability and antiproliferative activity of six fluorescent perylenemonoimide (PMIs) derivatives is reported. A positive charge seems to be the key to target G4. This study also reveals the importance of the element substitution in the potential biological activity of PMIs, being the polyethylene glycol (PEG) chains in the peri position responsible for their antiproliferative activity. Among them, the cationic PMI6 with two PEG chains is the most promising compound since its fluorescence is enhanced in the presence of G-quadruplex structures. Moreover, PMI6 binds to the human telomeric G-quadruplex hTelo with high affinity and displays a high antiproliferative potential towards HeLa (cervical adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian adenocarcinoma) cells. Its fate can be followed inside cells thanks to its fluorescent properties: the compound is found to accumulate in the mitochondria.
Chemistry Department University of Burgos Pza Misael Bañuelos s n 09001 Burgos Spain
Molecular Biology Institute of Barcelona IBMB CSIC 08028 Barcelona Spain
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