Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(ii) and Ir(iii) complexes with a 1,3,4-thiadiazole-based ligand

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26620%2F23%3APU150388" target="_blank" >RIV/00216305:26620/23:PU150388 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/23:73622017

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2023/dt/d3dt01696j" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2023/dt/d3dt01696j</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3dt01696j" target="_blank" >10.1039/d3dt01696j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(ii) and Ir(iii) complexes with a 1,3,4-thiadiazole-based ligand

Popis výsledku v původním jazyce

Half-sandwich complexes [Ru(?(6)-pcym)(L1)X]PF6 (1, 3) and [Ir(?(5)-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A H-1 NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD(+) with Ir(iii) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(ii) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(iii) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

Název v anglickém jazyce

Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(ii) and Ir(iii) complexes with a 1,3,4-thiadiazole-based ligand

Popis výsledku anglicky

Half-sandwich complexes [Ru(?(6)-pcym)(L1)X]PF6 (1, 3) and [Ir(?(5)-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A H-1 NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD(+) with Ir(iii) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(ii) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(iii) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

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

2023

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

52

Číslo periodika v rámci svazku

36

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

12717-12732

Kód UT WoS článku

001052933500001

EID výsledku v databázi Scopus

2-s2.0-85170226951