Platinum(IV)–Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple‐Negative Breast Cancer Models

Author:

López‐Hernández Javier E.12ORCID,Nayeem Nazia12ORCID,Cerón‐Carrasco José P.3ORCID,Ahad Afruja124ORCID,Hafeez Aiman1,León Ignacio E.5ORCID,Contel Maria12ORCID

Affiliation:

1. Department of Chemistry and Brooklyn College Cancer Center Brooklyn College The City University of New York Brooklyn NY, 11210 USA

2. Biology Chemistry and Biochemistry PhD Programs The Graduate Center The City University of New York New York NY, 10016 USA

3. Centro Universitario de la Defensa Universidad Politécnica de Cartagena C/Coronel López Peña s/n, Base Aérea de San Javier Santiago de la Ribera 30720 Murcia Spain

4. Radiology, Molecular Pharmacology Program, and Radiochemistry and Molecular Imaging Probes Core Memorial Sloan Kettering Cancer Center New York NY 11065 USA

5. Centro de Química Inorgánica CEQUINOR (CCT-CONICET La Plata, Asociado a CIC) Departamento de Química, Facultad de Ciencias Exactas Universidad Nacional de La Plata Blvd. 120 N°1465 La Plata 1900 Argentina

Abstract

AbstractNew heterometallic binuclear and trinuclear platinum(IV)–gold(I) compounds of the type [Pt(L)nCl2(OH){(OOC‐4‐C6H4‐PPh2)AuCl}x] (L=NH3, n=2; x=1, 2; L=diaminocyclohexane, DACH, n=1; x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu2 compound containing the PtIV core based on oxaliplatin, to further investigate its cell‐death pathway, cell and organelle uptake and anticancer effects against the triple‐negative breast cancer (TNBC) MDA‐MB‐231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties, and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents, but inhibit pro‐angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells.

Funder

National Institute of General Medical Sciences

Publisher

Wiley

Subject

General Chemistry,Catalysis,Organic Chemistry

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