Synthesis and photodynamic properties of pyrazole-indole hybrids in the human skin melanoma cell line G361
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00532929" target="_blank" >RIV/61389030:_____/20:00532929 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61989592:15110/20:73602382 RIV/61989592:15310/20:73602382
Výsledek na webu
<a href="http://doi.org/10.1016/j.dyepig.2020.108666" target="_blank" >http://doi.org/10.1016/j.dyepig.2020.108666</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.dyepig.2020.108666" target="_blank" >10.1016/j.dyepig.2020.108666</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Synthesis and photodynamic properties of pyrazole-indole hybrids in the human skin melanoma cell line G361
Popis výsledku v původním jazyce
Three conjugated pyrazole-indole hybrids, 5, 7 and 10, were synthesized from easily accessible 3-(hexyloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde 1 and 5-iodo-3,3-dimethyl-2-phenyl-3H-indole 4 employing olefination reactions (Wittig, Ramirez), Vilsmeier-Haack formylation and palladium-catalysed cross coupling reactions (ligand-free Heck, Sonogashira). The compounds displayed no cytotoxicity in the melanoma cell line G361 unless irradiated with visible blue light (414 nm), and the potency of the compounds increased with light intensity. Lead compound 7 displayed EC50 values of 3.08, 0.26 and 0.05 μM in cells irradiated with 1, 10 and 50 J/cm2, respectively. The following experiments revealed increased levels of reactive oxygen species in treated cells and a decrease in JC-1 polymer aggregation within the mitochondria, suggesting mitochondrial membrane depolarization. In addition, extensive DNA fragmentation was detected using the comet assay and by detection of phosphorylated histone H2A.X, the level of which increased with both increased compound concentration and irradiation energy. In control experiments, cells kept either in the dark or without compound 7 did not show any DNA damage. Overall, the results demonstrated that fluorescent pyrazole-indole hybrids may serve as an interesting source of photosensitizing compounds with anticancer activity.
Název v anglickém jazyce
Synthesis and photodynamic properties of pyrazole-indole hybrids in the human skin melanoma cell line G361
Popis výsledku anglicky
Three conjugated pyrazole-indole hybrids, 5, 7 and 10, were synthesized from easily accessible 3-(hexyloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde 1 and 5-iodo-3,3-dimethyl-2-phenyl-3H-indole 4 employing olefination reactions (Wittig, Ramirez), Vilsmeier-Haack formylation and palladium-catalysed cross coupling reactions (ligand-free Heck, Sonogashira). The compounds displayed no cytotoxicity in the melanoma cell line G361 unless irradiated with visible blue light (414 nm), and the potency of the compounds increased with light intensity. Lead compound 7 displayed EC50 values of 3.08, 0.26 and 0.05 μM in cells irradiated with 1, 10 and 50 J/cm2, respectively. The following experiments revealed increased levels of reactive oxygen species in treated cells and a decrease in JC-1 polymer aggregation within the mitochondria, suggesting mitochondrial membrane depolarization. In addition, extensive DNA fragmentation was detected using the comet assay and by detection of phosphorylated histone H2A.X, the level of which increased with both increased compound concentration and irradiation energy. In control experiments, cells kept either in the dark or without compound 7 did not show any DNA damage. Overall, the results demonstrated that fluorescent pyrazole-indole hybrids may serve as an interesting source of photosensitizing compounds with anticancer activity.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10601 - Cell biology
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Dyes and Pigments
ISSN
0143-7208
e-ISSN
1873-3743
Svazek periodika
183
Číslo periodika v rámci svazku
DEC
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
12
Strana od-do
108666
Kód UT WoS článku
000569771600010
EID výsledku v databázi Scopus
2-s2.0-85089688038