Cell and Cell‐Free Mechanistic Studies on Two Gold(III) Complexes with Proven Antitumor Properties

Reactions of Medicinal Gold(III) Compounds With Proteins and Peptides Explored by Electrospray Ionization Mass Spectrometry and Complementary Biophysical Methods

“…Notably, AuL12 was shown to behave as a prodrug upon releasing its bromide ligands (Pratesi et al, 2019). Significant oxidizing properties were also documented for this gold(III) complex (Nardon et al, 2017).…”

Antiproliferative effects of two gold(I)-N-heterocyclic carbene complexes in A2780 human ovarian cancer cells: a comparative proteomic study

“…As previously mentioned, investigations on the cytotoxicity scores of gold complexes were initially focused on auranofin and its analogues, which present linear gold phosphane structures [ 11 , 12 ]. More recently, a variety of gold derivatives has been tested as potential antitumor agents, including organogold derivatives, complexes with polydentate nitrogen donor ligands, gold porphyrins, gold dithiocarbamates, and gold-N-heterocyclic carbene (NHC) [ 13 – 17 ]. Based on the great structural variety of the used ligands and their role in controlling the reactivity of the gold centre, a unique mode of action or pharmacological profile is unlikely to exist.…”

Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations

“…[6] The poor chemotherapeutic index of this widely clinically used drug gave rise to the development of second-and third-generation platinum-based derivatives and opened the frontiers to the design of new anticancer drugs based on alternative metals. [11,12] These promising results represented the starting point for the development of new second generation compounds, designedt oi mprove bioavailability,t umor selectivity, andc ellular uptake [13][14][15] rela-Five new Au III -peptidodithiocarbamatoc omplexeso ft he type [Au III Br 2 (dtc-AA 1 -AA 2 -OR] (in which AA 1 = N-methylglycine (Sar), l/d-Pro;A A 2 = l/d-Ala, a-aminoisobutyric acid (Aib);R = OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/ort he chiral amino acid configuration, were designedt oe nhancet umor selectivity and bioavailability.T he gold(III)-based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptidet ransporters (namely PEPT1 and PEPT2), which are upregulated in severalt umor cells. [10] In our researchg roup, new first generation Au III -dithiocarbamato compounds with the general formula [Au III X 2 (dtc)] (X = Cl, Br;d tc = various dithiocarbamates) were designed and prepared.…”

“…[11] Moreover,n either cross-resistance nor the main drawbacks of cisplatin-based therapy were detected.I ndeed, in recenty ears, it was demonstrated that Au III -dithiocarbamato complexes exploit am echanism of action different from that of the clinically established platinum drugs. [11,12] These promising results represented the starting point for the development of new second generation compounds, designedt oi mprove bioavailability,t umor selectivity, andc ellular uptake [13][14][15] rela-Five new Au III -peptidodithiocarbamatoc omplexeso ft he type [Au III Br 2 (dtc-AA 1 -AA 2 -OR] (in which AA 1 = N-methylglycine (Sar), l/d-Pro;A A 2 = l/d-Ala, a-aminoisobutyric acid (Aib);R = OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/ort he chiral amino acid configuration, were designedt oe nhancet umor selectivity and bioavailability.T he gold(III)-based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptidet ransporters (namely PEPT1 and PEPT2), which are upregulated in severalt umor cells. The compounds were synthesized and fully characterized,m ainly by meanso fe lemental analysis,o ne-and two-dimensional NMR spectroscopy,F T-IR, and UV/Vis spectrophotometry.T he crystal structures of three compounds were also solved by X-ray diffraction.…”