Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73591068" target="_blank" >RIV/61989592:15310/18:73591068 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/pdf/10.1021/acs.organomet.8b00415" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acs.organomet.8b00415</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.organomet.8b00415" target="_blank" >10.1021/acs.organomet.8b00415</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids

Popis výsledku v původním jazyce

The half-sandwich iridium(III) complexes [Ir-(eta(5)-Cp-x)(phaza(-))Cl] (1, 2), [Ir(eta(5)-Cp-x)(thaza(-))Cl] (3, 4), and [Ir(eta(5)-Cp-x)(pyaza)Cl]PF6 (5, 6) containing deprotonated 1-phenyl-7-azaindole (phaza(-)) and 1-(thiophen-2-yl)-7-azaindole (thaza(-)) and electroneutral 1-(pyridin-2-yl)-7-azaindole (pyaza), were prepared; Cp-x = pentamethylcyclopentadienyl (Cp*; for 1, 3, and 5) or 1,2,3,4-tetramethyl-5-phenyl-cyclopentadienyl (Cp-Ph; for 2, 4, and 6). The complexes were thoroughly characterized, including a single-crystal X-ray analysis of complexes 1, 5, and 6. All of the complexes were screened for their in vitro cytotoxicity at the A2780 human ovarian carcinoma cell line and its A2780R cisplatin-resistant variant (2D culture cells). The best-performing complex 6 was further studied against the human DU-145 prostatic carcinoma, A549 lung carcinoma, HCT116 colon carcinoma, HeLa cervix adenocarcinoma, and MCF7 breast adenocarcinoma cell lines (2D culture cells). Complex 6 showed a cytotoxic profile different from that of cisplatin at the used cells, with the highest activity detected at the A2780, MCF7, and HCT116 cells (IC50 = 3.1, 6.9, and 10.4 mu M, respectively). Complex 6 exhibited relevant selectivity toward cancer cells (IC50 = 3.1-13.0 mu M) over the MRC-5 human noncancerous lung fibroblast cells (IC50 &gt; 50.0 mu M). Complex 6 was markedly more accumulated by the A2780 cells in comparison to cisplatin after 24 h exposure. Flow cytometry studies showed that the cell cycle of the A2780 cells treated by complex 6 is modified differently (G(0)/G(1), arrest) in comparison to cisplatin (G(2)/M arrest). Additionally to the monolayer (2D) cancer cell cultures, the cytotoxicity of complex 6 was for the first time among half-sandwich iridium(III) complexes also assessed at spheroid (3D) MCF7 cells, where its potency (IC50 = 22.9 mu M for complex 6) remained significantly better than that for the reference drug cisplatin (IC50 = 35.4 mu M).

Název v anglickém jazyce

Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids

Popis výsledku anglicky

The half-sandwich iridium(III) complexes [Ir-(eta(5)-Cp-x)(phaza(-))Cl] (1, 2), [Ir(eta(5)-Cp-x)(thaza(-))Cl] (3, 4), and [Ir(eta(5)-Cp-x)(pyaza)Cl]PF6 (5, 6) containing deprotonated 1-phenyl-7-azaindole (phaza(-)) and 1-(thiophen-2-yl)-7-azaindole (thaza(-)) and electroneutral 1-(pyridin-2-yl)-7-azaindole (pyaza), were prepared; Cp-x = pentamethylcyclopentadienyl (Cp*; for 1, 3, and 5) or 1,2,3,4-tetramethyl-5-phenyl-cyclopentadienyl (Cp-Ph; for 2, 4, and 6). The complexes were thoroughly characterized, including a single-crystal X-ray analysis of complexes 1, 5, and 6. All of the complexes were screened for their in vitro cytotoxicity at the A2780 human ovarian carcinoma cell line and its A2780R cisplatin-resistant variant (2D culture cells). The best-performing complex 6 was further studied against the human DU-145 prostatic carcinoma, A549 lung carcinoma, HCT116 colon carcinoma, HeLa cervix adenocarcinoma, and MCF7 breast adenocarcinoma cell lines (2D culture cells). Complex 6 showed a cytotoxic profile different from that of cisplatin at the used cells, with the highest activity detected at the A2780, MCF7, and HCT116 cells (IC50 = 3.1, 6.9, and 10.4 mu M, respectively). Complex 6 exhibited relevant selectivity toward cancer cells (IC50 = 3.1-13.0 mu M) over the MRC-5 human noncancerous lung fibroblast cells (IC50 &gt; 50.0 mu M). Complex 6 was markedly more accumulated by the A2780 cells in comparison to cisplatin after 24 h exposure. Flow cytometry studies showed that the cell cycle of the A2780 cells treated by complex 6 is modified differently (G(0)/G(1), arrest) in comparison to cisplatin (G(2)/M arrest). Additionally to the monolayer (2D) cancer cell cultures, the cytotoxicity of complex 6 was for the first time among half-sandwich iridium(III) complexes also assessed at spheroid (3D) MCF7 cells, where its potency (IC50 = 22.9 mu M for complex 6) remained significantly better than that for the reference drug cisplatin (IC50 = 35.4 mu M).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

ORGANOMETALLICS

ISSN

0276-7333

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

2749-2759

Kód UT WoS článku

000443526200013

EID výsledku v databázi Scopus

2-s2.0-85052704111