- Publikační typ
- abstrakt z konference MeSH
A novel series of trisubstituted acridines were synthesized with the aim of mimicking the effects of BRACO19. These compounds were synthesized by modifying the molecular structure of BRACO19 at positions 3 and 6 with heteroacyclic moieties. All of the derivatives presented in the study exhibited stabilizing effects on the human telomeric DNA quadruplex. UV-vis spectroscopy, circular dichroism, linear dichroism and viscosimetry were used in order to study the nature of the DNA binding in more detail. The results show that all of the novel derivatives were able to fold the single-stranded DNA sequences into antiparallel G-quadruplex structures, with derivative 15 exhibiting the highest stabilizing capability. Cell cycle analysis revealed that a primary trend of the "braco"-like derivatives was to arrest the cells in the S- and G2M-phases of the cell cycle within the first 72h, with derivative 13 and BRACO19 proving particularly effective in suppressing cell proliferation. All studies derivatives were less toxic to human fibroblast cell line in comparison with HT 29 cancer cell line.
- MeSH
- akridiny chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie MeSH
- buněčné linie MeSH
- buněčný cyklus účinky léků MeSH
- DNA chemie metabolismus MeSH
- G-kvadruplexy účinky léků MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie metabolismus MeSH
- proliferace buněk účinky léků MeSH
- simulace molekulového dockingu MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Synovial membrane and synovial fluid represent a good source of mesenchymal stem cells. They have been regarded as a promising therapeutic tool for musculoskeletal regeneration. Synovium-derived mesenchymal stem cells have higher expression of CD44 and better chondrogenic potential in vitro than mesenchymal stem cells from other tissues. In this study we compared mesenchymal stem cells from synovium and synovial fluid on the base of morphological, immunophenotype and differentiation features. A heterogeneous population of cells with different morphology was obtained after isolation and 4-day cultivation. The mesenchymal stem cell immunophenotype was confirmed by positive expression of CD105, CD90, and CD44 by flow cytometry and cells were negative for CD45. CD105+ cells were selected by immunomagnetic separation after 2–4 weeks of cultivation. The percentage of CD105+ cells in the mesenchymal stem cell population from synovia was between 40–50 % before immunomagnetic separation and increased to 95 % following the immunomagnetic separation. Von Kossa, Alcian blue and Oil Red O staining was used to assess the differentiation potential of synovial mesenchymal stem cells. Long-term cultivation did not affect the morphology and immunophenotype of synovial mesenchymal stem cells. Our results confirmed that immunomagnetic separation based on CD 105 antigen is a suitable method to enrich the subpopulation of CD105+ synovial mesenchymal stem cells.
- MeSH
- buněčná diferenciace MeSH
- buněčný rodokmen MeSH
- CD antigeny metabolismus MeSH
- chondrocyty cytologie MeSH
- chondrogeneze MeSH
- imunofenotypizace MeSH
- imunomagnetická separace metody MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie metabolismus MeSH
- průtoková cytometrie MeSH
- receptory buněčného povrchu metabolismus MeSH
- separace buněk metody MeSH
- synoviální membrána cytologie MeSH
- synoviální tekutina cytologie MeSH
- Check Tag
- lidé MeSH