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

LOPEZ-HERNANDEZ, JAVIER E.; NAYEEM, NAZIA; CERÓN-CARRASCO, JOSÉ P.; LAHAD, AFRUJA; HAFEED, AIMAN; LEÓN, IGNACIO E.; CONTEL, MARIA

CHEMISTRY-A EUROPEAN JOURNAL

WILEY-V C H VERLAG GMBH

Año: 2023

0947-6539

New heterometallic binuclear and trinuclear platinum(IV)gold(I)compounds of the type [Pt(L)nCl2(OH){(OOC-4-CPPh2)AuCl}x] (L=NH, n = 2; x = 1,2; L = diaminocyclohexane, DACH,n = 1; x = 2) are described. These compounds are cytotoxic andselective against a small panel of renal, bladder, ovarian and breastcancer cell lines. We selected a trinuclear PtAu3 compound containingthe Pt(IV) core based on oxaliplatin, to further investigate its cell deathpathway, cell and organelle uptake and anticancer effects againsttriple negative breast cancer (TNBC) MDA-MB-231 cell line. Thiscompound induces apoptosis and accumulates mainly in the nucleusand mitochondria. It also exerts remarkable antimigratory andantiangiogenic properties, and has a potent cytotoxic effect againstTNBC 3D spheroids. Trinuclear compounds do not seem to displayrelevant interactions with calf thymus (CT) DNA and plasmid(pBR322) even in the presence of reducing agents, but inhibit proangiogenicenzymethioredoxinreductase(TrxR)inTNBCcells.