Biotin functionalization of 8-hydroxyquinoline anticancer organometallics: low toxicity but potent activity.

[M(arene)(HQ)Cl] complexes (M = Ru/Os/Rh/Ir; HQ = 8-hydroxyquinoline) have shown promise as anticancer agents. To assess the effect of conjugating biotin (vitamin B7) to such compounds and improve their tumor-targeting ability through interaction with the sodium-dependent multivitamin transporter (SMVT), the chlorido co-ligand was exchanged with biotinylated 6-aminoindazole. The complexes were characterized by NMR spectroscopy and mass spectrometry, and purity was determined by elemental analysis.

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand.

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs and organometallic half-sandwich moieties.

Incorporation of β-Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels, DNA Cleavage and Antiproliferative Activity.

Redox-active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades.

Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs.

Proteomics has played an important role in elucidating the fundamental processes occuring in living cells. Translating these methods to metallodrug research ('metalloproteomics') has provided a means for molecular target identification of metal-based anticancer agents which should signifcantly advance the research field. In combination with biological assays, these techniques have enabled the mechanisms of action of metallodrugs to be linked to their interactions with molecular targets and aid understanding of their biological properties.

Potent Inhibition of Thioredoxin Reductase by the Rh Derivatives of Anticancer M(arene/Cp*)(NHC)Cl Complexes.

Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with -heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation of Rh- and Ir(Cp*)(NHC)Cl (Cp* = η-pentamethylcyclopentadienyl) compounds and comparison of their properties to the Ru- and Os(cym) analogues (cym = η--cymene). Like the Ru- and Os(cym) complexes, the Rh- and Ir(Cp*) derivatives exhibit cytotoxic activity with half maximal inhibitory concentration (IC) values in the low micromolar range against a set of four human cancer cell lines.

Anticancer organorhodium and -iridium complexes with low toxicity in vivo but high potency in vitro: DNA damage, reactive oxygen species formation, and haemolytic activity.

Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear RhIII(Cp*) and IrIII(Cp*) complexes that have in vitro anticancer activity superior to cisplatin and the investigational drug IT-139, while being less toxic in haemolysis and in vivo zebrafish models. The mode of action appears to be related to DNA damage and ROS-mediated stress pathways.

Hydroxyquinoline-derived anticancer organometallics: Introduction of amphiphilic PTA as an ancillary ligand increases their aqueous solubility.

Organometallic compounds based on bioactive ligand systems have shown promising antiproliferative properties. The use of 8-hydroxyquinoline and its derivatives as bioactive ligands resulted in organometallic complexes with potent anticancer activity, but they lack aqueous solubility for further development. We report here the preparation of a series of M(cym/Cp*)Cl complexes (η-p-cymene (cym): M = Ru, Os; η-pentamethylcyclopentadienyl (Cp*): M = Rh, Ir) with hydroxyquinoline-derived co-ligands and in a subsequent step the substitution of the chlorido ligands for amphiphilic 1,3,5-triaza-7-phosphatricyclo-[3.