Identification of potent anticancer copper(II) complexes containing tripodal bis[2-ethyl-di(3,5- dialkyl-1H-pyrazol-1-yl)]amine moiety

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F21%3A73609061" target="_blank" >RIV/61989592:15640/21:73609061 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/21:73609061

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2021/DT/D1DT01724A" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2021/DT/D1DT01724A</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d1dt01724a" target="_blank" >10.1039/d1dt01724a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of potent anticancer copper(II) complexes containing tripodal bis[2-ethyl-di(3,5- dialkyl-1H-pyrazol-1-yl)]amine moiety

Popis výsledku v původním jazyce

A series of heteroleptic copper(II) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L-1), (bis(2-ethyl-d i (3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L-2), [bis(2-ethyl-di (3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L-3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L-4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L-5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L-1)Cl]PF6 (1-PF6), [Cu(L-2)Cl]ClO4 (2-ClO4) and [Cu(L-3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 mu M, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 mu M). The complexes [Cu(L-4)Cl]PF6 (4-PF6) and [Cu(L-5)Cl]PF6 (5-PF6 ) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 mu M, and 33.8 mu M, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.

Název v anglickém jazyce

Identification of potent anticancer copper(II) complexes containing tripodal bis[2-ethyl-di(3,5- dialkyl-1H-pyrazol-1-yl)]amine moiety

Popis výsledku anglicky

A series of heteroleptic copper(II) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L-1), (bis(2-ethyl-d i (3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L-2), [bis(2-ethyl-di (3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L-3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L-4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L-5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L-1)Cl]PF6 (1-PF6), [Cu(L-2)Cl]ClO4 (2-ClO4) and [Cu(L-3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 mu M, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 mu M). The complexes [Cu(L-4)Cl]PF6 (4-PF6) and [Cu(L-5)Cl]PF6 (5-PF6 ) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 mu M, and 33.8 mu M, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologie pro budoucnost</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Dalton Transactions

ISSN

1477-9226

e-ISSN

—

Svazek periodika

50

Číslo periodika v rámci svazku

33

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

11521-11534

Kód UT WoS článku

000680877300001

EID výsledku v databázi Scopus

2-s2.0-85113706204