Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells

0574516 - BFÚ 2024 RIV US eng J - Journal Article
Novohradský, Vojtěch - Marco, A. - Marková, Lenka - Cutillas, N. - Ruiz, J. - Brabec, Viktor
Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells.
Journal of Medicinal Chemistry. Roč. 66, č. 14 (2023), s. 9766-9783. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR(CZ) GA23-06307S
Institutional support: RVO:68081707
Keywords : EPITHELIAL-MESENCHYMAL TRANSITION * IRIDIUM(III) COMPLEXES * CHEMOTHERAPY
OECD category: Inorganic and nuclear chemistry
Impact factor: 7.3, year: 2022
Method of publishing: Open access
https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00586

Herein, we report a series of new octahedral iridium(III)complexes Ir1-Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF6 (N^N^N = 4 & PRIME,-(p-tolyl)-2,2 & PRIME,:6 & PRIME,,2 & DPRIME,-terpyridine,C^N = deprotonated 2-arylbenzimidazole backbone) to introduce newmetal-based compounds for effective inhibition of metastatic processesin triple-negative breast cancer (TNBC). The results show that thestructural modifications within the C^N scaffold strongly impact theantimetastatic properties of these complexes in TNBC cells. Furthermore,testing the antimetastatic effects of the investigated Ir complexesrevealed that the highest antimetastatic activity in TNBC cells isexhibited by complex Ir1. This result was in contrastto the effects of the clinically used drug doxorubicin used in conventionalchemotherapy of TNBC, which conversely promoted metastatic propertiesof TNBC cells. Thus, the latter result suggests that doxorubicin chemotherapymay increase the risk of metastasis of breast cancer cells, so thesearch for new drugs to treat breast cancer that would show betterantitumor effects than doxorubicin is justified.
Permanent Link: https://hdl.handle.net/11104/0350069