Newly developed organoiridium(III) complexes containing N,P-ligands possess antiproliferative activity in selected cancer cell lines
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F24%3AN0000237" target="_blank" >RIV/00027162:_____/24:N0000237 - isvavai.cz</a>
Výsledek na webu
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DOI - Digital Object Identifier
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Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Newly developed organoiridium(III) complexes containing N,P-ligands possess antiproliferative activity in selected cancer cell lines
Popis výsledku v původním jazyce
The result is the contribution "Newly developed organoiridium(III) complexes containing N,P-ligands possess antiproliferative activity in selected cancer cell lines", presented in the form of a poster at the AACR Annual Meeting 2024 (American Association for Cancer Research), held in San Diego, USA, from April 5–12, 2024. A total of 30,000 scientists from around the world in the field of cancer research attended the conference, along with thousands of exhibitors, posters, and lectures. In conventional cancer treatment, platinum-based cytostatics are considered as standard therapy; however, they possess severe side effects. This fact leads to a constant effort to develop new non-platinum metallodrugs with different mechanism of action (MoA). In our study we developed new half-sandwich organoiridium(III) complexes, of general formulas [Ir(η5-Cp*)Cl(LNP)]PF6 (1-3) and [Ir(η5-Cpph)Cl(LNP)]PF6 (4-6) involving three different N,P-donor phosphinoalkylamines (LNP), which we tested on 2D and 3D cancer models; HCp* = pentamethylcyclopentadiene, HCpph= (2,3,4,5-tetramethylcyclopenta-2,4-dien-1-yl)benzene. The most effective complexes 3 and 6 bearing 3-(diphenylphosphanyl)propan-1-amine had the highest cytotoxic effect against various cancer cell lines (THP-1, HeLa, SW982, A549, MOR) including a cisplatin-resistant lung carcinoma cell line (MOR/CPR) with IC50 values between 3.1 and 9.1 μM for specific cell lines. The cytotoxic effect was further demonstrated on 3D spheroids of lung cancer cells that revealed anti-cancer and anti-migration potential of complexes 3 and 6. Cell cycle and cell death analysis showed a different mechanism compared to the effect of cisplatin. Moreover, complex 3 did not decrease cell viability of non-cancerous cells (peripheral blood mononuclear cells and porcine chondrocytes) under 50% at a concentration of 20 µM. In addition, we report for the first time that organoiridium complexes showed high cytotoxic activity on cancer cell lines, including cisplatin-resistant cell line, with different MoA from cisplatin. They trigger expression of stress-related genes associated with oxidative stress, DNA damage, and endoplasmic reticulum stress and, moreover, complex 3 showed cytotoxic selectivity towards cancer cells.
Název v anglickém jazyce
Newly developed organoiridium(III) complexes containing N,P-ligands possess antiproliferative activity in selected cancer cell lines
Popis výsledku anglicky
The result is the contribution "Newly developed organoiridium(III) complexes containing N,P-ligands possess antiproliferative activity in selected cancer cell lines", presented in the form of a poster at the AACR Annual Meeting 2024 (American Association for Cancer Research), held in San Diego, USA, from April 5–12, 2024. A total of 30,000 scientists from around the world in the field of cancer research attended the conference, along with thousands of exhibitors, posters, and lectures. In conventional cancer treatment, platinum-based cytostatics are considered as standard therapy; however, they possess severe side effects. This fact leads to a constant effort to develop new non-platinum metallodrugs with different mechanism of action (MoA). In our study we developed new half-sandwich organoiridium(III) complexes, of general formulas [Ir(η5-Cp*)Cl(LNP)]PF6 (1-3) and [Ir(η5-Cpph)Cl(LNP)]PF6 (4-6) involving three different N,P-donor phosphinoalkylamines (LNP), which we tested on 2D and 3D cancer models; HCp* = pentamethylcyclopentadiene, HCpph= (2,3,4,5-tetramethylcyclopenta-2,4-dien-1-yl)benzene. The most effective complexes 3 and 6 bearing 3-(diphenylphosphanyl)propan-1-amine had the highest cytotoxic effect against various cancer cell lines (THP-1, HeLa, SW982, A549, MOR) including a cisplatin-resistant lung carcinoma cell line (MOR/CPR) with IC50 values between 3.1 and 9.1 μM for specific cell lines. The cytotoxic effect was further demonstrated on 3D spheroids of lung cancer cells that revealed anti-cancer and anti-migration potential of complexes 3 and 6. Cell cycle and cell death analysis showed a different mechanism compared to the effect of cisplatin. Moreover, complex 3 did not decrease cell viability of non-cancerous cells (peripheral blood mononuclear cells and porcine chondrocytes) under 50% at a concentration of 20 µM. In addition, we report for the first time that organoiridium complexes showed high cytotoxic activity on cancer cell lines, including cisplatin-resistant cell line, with different MoA from cisplatin. They trigger expression of stress-related genes associated with oxidative stress, DNA damage, and endoplasmic reticulum stress and, moreover, complex 3 showed cytotoxic selectivity towards cancer cells.
Klasifikace
Druh
O - Ostatní výsledky
CEP obor
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OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
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)
Ostatní
Rok uplatnění
2024
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů