Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F24%3A73625469" target="_blank" >RIV/61989592:15310/24:73625469 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/24:73625469

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2024/dt/d4dt00942h" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/dt/d4dt00942h</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4dt00942h" target="_blank" >10.1039/d4dt00942h</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects

Popis výsledku v původním jazyce

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn-2(L-1)(2)](ClO4)(2)MeOH (1), [Zn-2(L-2)(2)](ClO4)(2) (2), and four mononuclear [Zn(L-3)(H2O)]MeOH (3), [Zn(L-4)] (4), [Zn(L-5)] (5) and [Zn(L-6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 mu M), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 approximate to 16.3-19.5 mu M) over MRC-5 ones (with IC50 &gt;50 mu M for 1, 2 and 4, and with IC50 &gt;25 mu M for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

Název v anglickém jazyce

Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects

Popis výsledku anglicky

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn-2(L-1)(2)](ClO4)(2)MeOH (1), [Zn-2(L-2)(2)](ClO4)(2) (2), and four mononuclear [Zn(L-3)(H2O)]MeOH (3), [Zn(L-4)] (4), [Zn(L-5)] (5) and [Zn(L-6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 mu M), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 approximate to 16.3-19.5 mu M) over MRC-5 ones (with IC50 &gt;50 mu M for 1, 2 and 4, and with IC50 &gt;25 mu M for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

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

1477-9234

Svazek periodika

53

Číslo periodika v rámci svazku

29

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

20

Strana od-do

"12261 "- 12280

Kód UT WoS článku

001268308800001

EID výsledku v databázi Scopus

2-s2.0-85198054281