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

Vojtěch Novohradský, Alicia Marco, Lenka Marková, N. Cutillas, José Ruiz, Viktor Brabec

2023Journal of Medicinal Chemistry22 citationsDOIOpen Access PDF

Abstract

High Resolution Image Download MS PowerPoint Slide Herein, we report a series of new octahedral iridium(III) complexes Ir1 – Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF 6 (N^N^N = 4′-( p -tolyl)-2,2′:6′,2″-terpyridine; C^N = deprotonated 2-arylbenzimidazole backbone) to introduce new metal-based compounds for effective inhibition of metastatic processes in triple-negative breast cancer (TNBC). The results show that the structural modifications within the C^N scaffold strongly impact the antimetastatic properties of these complexes in TNBC cells. Furthermore, testing the antimetastatic effects of the investigated Ir complexes revealed that the highest antimetastatic activity in TNBC cells is exhibited by complex Ir1 . This result was in contrast to the effects of the clinically used drug doxorubicin used in conventional chemotherapy of TNBC, which conversely promoted metastatic properties of TNBC cells. Thus, the latter result suggests that doxorubicin chemotherapy may increase the risk of metastasis of breast cancer cells, so the search for new drugs to treat breast cancer that would show better antitumor effects than doxorubicin is justified.

Topics & Concepts

ChemistryTriple-negative breast cancerLigand (biochemistry)CancerCancer researchStereochemistryBreast cancerCombinatorial chemistryPharmacologyBiochemistryReceptorInternal medicineMedicineBiologyMetal complexes synthesis and propertiesClick Chemistry and ApplicationsSynthesis and biological activity
Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells | Litcius