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Novel quinazolin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity
M. Pospisilova, M. Andrs, M. Seifrtova, R. Havelek, D. Jun, P. Tomsik, L. Prchal, R. Dolezal, A. Tichy, T. Kucera, J. Korabecny, M. Rezacova,
Bioorganic chemistry.
2019 ;
82 (-) :
204-210.
[pub] 20181006
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc19034963
- MeSH
- apoptóza účinky léků MeSH
- buňky HT-29 MeSH
- chinazolinony chemická syntéza farmakologie toxicita MeSH
- doxorubicin farmakologie MeSH
- inhibitory enzymů chemická syntéza farmakologie toxicita MeSH
- jaderné proteiny antagonisté a inhibitory MeSH
- lidé MeSH
- morfoliny chemická syntéza farmakologie toxicita MeSH
- myši MeSH
- outbrední kmeny zvířat MeSH
- poly(ADP-ribosa)polymerasa 1 antagonisté a inhibitory MeSH
- proliferace buněk účinky léků MeSH
- proteinkinasa aktivovaná DNA antagonisté a inhibitory MeSH
- protinádorové látky farmakologie MeSH
- racionální návrh léčiv MeSH
- synergismus léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We report the design, synthesis and biological evaluation of 17 novel 8-aryl-2-morpholino-3,4-dihydroquinazoline derivatives based on the standard model of DNA-PK and PI3K inhibitors. Novel compounds are sub-divided into two series where the second series of five derivatives was designed to have a better solubility profile over the first one. A combination of in vitro and in silico techniques suggested a plausible synergistic effect with doxorubicin of the most potent compound 14d on cell proliferation via DNA-PK and poly(ADP-ribose) polymerase-1 (PARP-1) inhibition, while alone having a negligible effect on cell proliferation.
Citace poskytuje Crossref.org
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- $a Pospisilova, Monika $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, 500 03 Hradec Kralove, Czech Republic.
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- $a Rezacova, Martina $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, 500 03 Hradec Kralove, Czech Republic. Electronic address: rezacovaM@lfhk.cuni.cz.
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