Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25960253
DOI
10.1016/j.ejps.2015.04.023
PII: S0928-0987(15)00178-5
Knihovny.cz E-zdroje
- Klíčová slova
- Acridine derivatives, DNA-binding, HL-60 cells, Topoisomerases I and II,
- MeSH
- akridiny chemická syntéza metabolismus farmakologie MeSH
- akutní promyelocytární leukemie farmakoterapie enzymologie patologie MeSH
- časové faktory MeSH
- denaturace nukleových kyselin MeSH
- DNA-topoisomerasy I metabolismus MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- DNA chemie metabolismus MeSH
- farmaceutická chemie MeSH
- farmaceutická technologie metody MeSH
- fluorescenční spektrometrie MeSH
- HL-60 buňky MeSH
- inhibitory topoisomerasy I chemická syntéza metabolismus farmakologie MeSH
- inhibitory topoisomerasy II chemická syntéza metabolismus farmakologie MeSH
- konformace nukleové kyseliny MeSH
- kontrolní body buněčného cyklu účinky léků MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- proliferace buněk účinky léků MeSH
- spektrofotometrie ultrafialová MeSH
- viabilita buněk účinky léků MeSH
- viskozita MeSH
- vysoká teplota MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akridiny MeSH
- calf thymus DNA MeSH Prohlížeč
- DNA-topoisomerasy I MeSH
- DNA-topoisomerasy typu II MeSH
- DNA MeSH
- inhibitory topoisomerasy I MeSH
- inhibitory topoisomerasy II MeSH
- TOP1 protein, human MeSH Prohlížeč
HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K=3.1×10(4)-2.0×10(3)M(-1)). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5μM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution.
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