Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids
Original language description
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 > 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).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10402 - Inorganic and nuclear chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ORGANOMETALLICS
ISSN
0276-7333
e-ISSN
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Volume of the periodical
37
Issue of the periodical within the volume
16
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
2749-2759
UT code for WoS article
000443526200013
EID of the result in the Scopus database
2-s2.0-85052704111