Iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents
Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
Dalton transactions (Cambridge, England : 2003) - 51(2022), 14 vom: 05. Apr., Seite 5494-5514 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kar, Binoy [VerfasserIn] |
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| Links: |
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| Themen: |
339NCG44TV |
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| Anmerkungen: |
Date Completed 06.04.2022 Date Revised 06.04.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d2dt00168c |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM338245960 |
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| 520 | |a Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest | ||
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| 700 | 1 | |a Sharma S, Ajay |e verfasserin |4 aut | |
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| 700 | 1 | |a Bose, Bipasha |e verfasserin |4 aut | |
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