Cyclometalated Benzimidazole Osmium(II) Complexes with Antiproliferative Activity in Cancer Cells Disrupt Calcium Homeostasis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00572135" target="_blank" >RIV/68081707:_____/23:00572135 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/23:73620578

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.inorgchem.3c00501" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.inorgchem.3c00501</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.inorgchem.3c00501" target="_blank" >10.1021/acs.inorgchem.3c00501</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cyclometalated Benzimidazole Osmium(II) Complexes with Antiproliferative Activity in Cancer Cells Disrupt Calcium Homeostasis

Popis výsledku v původním jazyce

We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C<^>N)(N<^>N)2]OTf (N<^>N = 2,2 '-bipyridine and dipyrido[3,2-d:2 ',3 '-f]quinoxaline, C<^>N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C<^>N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiprolifer-ative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.

Název v anglickém jazyce

Cyclometalated Benzimidazole Osmium(II) Complexes with Antiproliferative Activity in Cancer Cells Disrupt Calcium Homeostasis

Popis výsledku anglicky

We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C<^>N)(N<^>N)2]OTf (N<^>N = 2,2 '-bipyridine and dipyrido[3,2-d:2 ',3 '-f]quinoxaline, C<^>N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C<^>N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiprolifer-ative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.

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/GA23-06316S" target="_blank" >GA23-06316S: Lékařská biofyzika a biochemie světlem-aktivovatelných metalofamak pro cílenou protinádorovou terapii.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Inorganic Chemistry

ISSN

0020-1669

e-ISSN

1520-510X

Svazek periodika

62

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

6474-6487

Kód UT WoS článku

000970111900001

EID výsledku v databázi Scopus

2-s2.0-85152663925