Synthesis, Characterization, and Comparative in Vitro Cytotoxicity Studies of Platinum(II), Palladium(II), and Gold(III) Methylsarcosinedithiocarbamate Complexes

This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determined by growth inhibition and apoptosis induction, has been investigated in both human leukemic promyelocites HL60 and human squamous cervical adenocarcinoma HeLa cell lines, and their activity has been compared to the well-known platinum-based anticancer agent cisplatin. On the basis of these experimental results, [Pd(MSDT)X]n (MSDT = methylsarcosinedithiocarbamate; X = Cl, Br) complexes show a strong dose-dependent growth inhibition of both HL60 and HeLa cells, with IC50 values slightly higher than those recorded for cisplatin; moreover, [Au(MSDT)X2] activity appears significantly higher or, at least, comparable to that of the reference drug. Exposure of both cell lines to [Pd(MSDT)X]n and [Au(MSDT)X2] complexes induces apoptosis, as determined by an Apo2.7 assay

Figure S1 from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Figure S1. Lipoplatin activity in A2780 and A2780cis cells</p

Figure S2 from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Figure S2. Cisplatin activity in A2780, A2780cis and OVCAR5 cells</p

Figure S3 from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Figure S3. Cisplatin activity in SKOV3 spheroids and OVCAR5 tumor xenograft</p

Supplementary materials from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Supplementary Materials and Methods, Legends to Figures S1, S2 and S3, References</p

Table S1 from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Table S1. Combination index (CI) values for OVCAR5 and SKOV3 cell lines treated with Cisplatin and Doxorubicin, Abraxane, Docetaxel or Paclitaxel.</p

Table S2 from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Table S2. Combination index (CI) values for OVCAR5 and SKOV3 cell lines treated with Carboplatin and Doxorubicin, Abraxane, Docetaxel or Paclitaxel.</p

Conflict of Interest Form Aldinucci D from Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Conflict of Interest Form</p

Design, Synthesis, and Preclinical Activity in Ovarian Cancer Models of New Phosphanegold(I)-N-heterocyclic Carbene Complexes

A new series of seven gold(I) complexes (1–7) containing 1,3-bis(2,6-diisopropylphenyl)­imidazol-2-ylidene (IPr) and phosphane ligands (L1–L7) were synthesized and evaluated for antitumor activity in ovarian cancer (OvCa) models. The synthesized complexes were characterized by IR, mass spectrometry and NMR spectroscopy, and complex 6 was characterized by XRD crystallography. The antiproliferative effect of the new complexes (1–7) was found to be higher than cisplatin and auranofin in OvCa cells sensitive and resistant to cisplatin. The anticancer activity of the most active complex 6 was investigated using OvCa in vitro models, including three-dimensional (3D) multicellular tumor spheroids and in vivo tumor xenografts. Both cisplatin and auranofin were used for comparative purposes. Complex 6 induced apoptosis, mitochondrial reactive oxygen species, and DNA damage; caused a G1 phase cell cycle arrest, inhibited proteasome activity, and cell migration; modified actin polymerization; and significantly inhibited OvCa murine xenografts. These promising results suggest further preclinical testing of these complexes for future applications

Toward the Selective Delivery of Chemotherapeutics into Tumor Cells by Targeting Peptide Transporters: Tailored Gold-Based Anticancer Peptidomimetics

Complexes [Au^IIIX₂(dtc-Sar-AA-O­(<i>t</i>-Bu))] (AA = Gly, X = Br (<b>1</b>)/Cl (<b>2</b>); AA = Aib, X = Br (<b>3</b>)/Cl (<b>4</b>); AA = l-Phe, X = Br (<b>5</b>)/Cl (<b>6</b>)) were designed on purpose in order to obtain gold­(III)-based anticancer peptidomimetics that might specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy, and the crystal structure of [Au^IIIBr₂(dtc-Sar-Aib-O­(<i>t</i>-Bu))] (<b>3</b>) was solved and refined. According to in vitro cytotoxicity studies, the Aib-containing complexes <b>3</b> and <b>4</b> turned out to be the most effective toward all the human tumor cell lines evaluated (PC3, DU145, 2008, C13, and L540), reporting IC₅₀ values much lower than that of cisplatin. Remarkably, they showed no cross-resistance with cisplatin itself and were proved to inhibit tumor cell proliferation by inducing either apoptosis or late apoptosis/necrosis depending on the cell lines. Biological results are here reported and discussed in terms of the structure–activity relationship