Organoiridium(III) complexes containing N,P-ligands and their antiproliferative activity in 2D and 3D cell-based models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F23%3AN0000193" target="_blank" >RIV/00027162:_____/23:N0000193 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Organoiridium(III) complexes containing N,P-ligands and their antiproliferative activity in 2D and 3D cell-based models

Popis výsledku v původním jazyce

Platinum-based cytostatic drugs are taken as etalon in the cancer therapy; however, they possess many adverse side effects. This fact leads to the developing of new non-platinum metallodrugs with different mechanism of action (MoA). One such group is represented by half-sandwich iridium(III) complexes, which offer high antiproliferative activity and different MoA than conventional platinum-based drugs. Herein we report on a series of [Ir(η5 Cp*)Cl(LNP)]PF6 (1–3) and [Ir(η5 Cpph)Cl(LNP)]PF6 (4–6) complexes involving three different N,P-donor phosphinoalkylamines (LNP); HCp* = pentamethylcyclopentadiene and HCpph = (2,3,4,5-tetramethylcyclopenta-2,4-dien-1-yl)benzene. The most potent complexes 3 and 6 bearing 3-(diphenylphosphanyl)propan-1-amine possessed the highest cytotoxic effect against different cancer cell lines (THP-1, HeLa, SW982, A549, MOR) including cisplatin-resistant lung carcinoma cell line (MOR/CPR) (IC50 values lie between 3.1 and 9.1 μM for particular cell lines). On the other hand, complex 3, but not 6, did not decrease cell viability of non-cancerous cells (chondrocytes, PBMCs) under 50% at the concentration of 20 µM. The cytotoxic effect was further demonstrated on 3D lung cancer cell spheroids, which revealed anti-cancer and anti-migration potential of complexes 3 and 6. The cell cycle and the cell death analyses showed a different mechanism in comparison with the effect of cisplatin. Moreover, we described for the first time that organoiridium complexes trigger the expression of stress-related genes connected with oxidative stress, DNA damage, and endoplasmic reticulum stress.

Název v anglickém jazyce

Organoiridium(III) complexes containing N,P-ligands and their antiproliferative activity in 2D and 3D cell-based models

Popis výsledku anglicky

Platinum-based cytostatic drugs are taken as etalon in the cancer therapy; however, they possess many adverse side effects. This fact leads to the developing of new non-platinum metallodrugs with different mechanism of action (MoA). One such group is represented by half-sandwich iridium(III) complexes, which offer high antiproliferative activity and different MoA than conventional platinum-based drugs. Herein we report on a series of [Ir(η5 Cp*)Cl(LNP)]PF6 (1–3) and [Ir(η5 Cpph)Cl(LNP)]PF6 (4–6) complexes involving three different N,P-donor phosphinoalkylamines (LNP); HCp* = pentamethylcyclopentadiene and HCpph = (2,3,4,5-tetramethylcyclopenta-2,4-dien-1-yl)benzene. The most potent complexes 3 and 6 bearing 3-(diphenylphosphanyl)propan-1-amine possessed the highest cytotoxic effect against different cancer cell lines (THP-1, HeLa, SW982, A549, MOR) including cisplatin-resistant lung carcinoma cell line (MOR/CPR) (IC50 values lie between 3.1 and 9.1 μM for particular cell lines). On the other hand, complex 3, but not 6, did not decrease cell viability of non-cancerous cells (chondrocytes, PBMCs) under 50% at the concentration of 20 µM. The cytotoxic effect was further demonstrated on 3D lung cancer cell spheroids, which revealed anti-cancer and anti-migration potential of complexes 3 and 6. The cell cycle and the cell death analyses showed a different mechanism in comparison with the effect of cisplatin. Moreover, we described for the first time that organoiridium complexes trigger the expression of stress-related genes connected with oxidative stress, DNA damage, and endoplasmic reticulum stress.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/NU22-08-00236" target="_blank" >NU22-08-00236: Preklinické studie neplatinových metaloléčiv v terapii rakoviny plic</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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