Unexpected structural preference with metallophilic Ag-Au contacts in silver(I)-N-heterocyclic carbene cluster; experimental and theoretical approach.

A novel synthetic donor-atom-selective approach has been adopted for the synthesis of a heterobimetallic cluster of a new NCN-pincer, 1,3-bis-(1-methyl-1H-benzo[d]imidazol-2-yl-methyl)-1H-imidazol-3-ium hexafluorophosphate (1·HPF6). The complex [Ag3(1)3][PF6]3 (2) has been prepared via the Ag2O route; which undergoes transmetallation to yield a cluster that seems to be the first example of the heterobimetallic trinuclear system [Au-Ag2(1)2Cl][PF6]2, 3. Finally, the trinuclear cluster geometries of 2 and 3 were confirmed via SCXRD studies. Interestingly, Au(I) binds preferentially with soft donor Ccarbene, which transmetallated from the cluster of 2. In both the cyclic trinuclear clusters, the M-M interactions were further inspected using gauge independent atomic orbital (GIAO) computations. Both 2 and 3 are luminescent and possess σ-aromaticity; the NICS values indicate that 3 is more aromatic than 2.

Dinuclear gold(I) complexes based on carbene and diphosphane ligands: bis[2-(dicyclohexylphosphano)ethyl]amine complex inhibits the proteasome activity, decreases stem cell markers and spheroid viability in lung cancer cells.

Three new dinuclear gold(I) complexes (1-3) containing a carbene (1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene (IPr)) and diphosphane ligands [bis(1,2-diphenylphosphano)ethane (Dppe), bis(1,3-diphenylphosphano)propane (Dppp) and bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA)], were synthesized and characterized by elemental analysis and, ESI-MS, mid FT-IR and NMR spectroscopic methods. The structures of complexes 2 and 3 were determined by X-ray crystallography, which revealed that the complexes are dinuclear having gold(I) ions linearly coordinated. The anticancer activities of the complexes (1-3) were evaluated in lung (A549), breast (MC-F7), prostate (PC-3), osteosarcoma (MG-63) and ovarian (A2780 and A2780cis) cancer models. Growth inhibition by the new complexes was higher than cisplatin in all cell lines tested. The mechanism of action of complex 3 was investigated in A549 cells using 2-dimensional (2D) models and 3D-multicellular tumor spheroids. Treatment of A549 cells with complex 3 caused: the induction of apoptosis and the generation of reactive oxygen species; the cell cycle arrest in the G0/G1 phase; the inhibition of both the proteasome and the NF-kB activity; the down-regulation of lung cancer stem cell markers (NOTCH1, CD133, ALDH1 and CD44). Complex 3 was more active than cisplatin also in 3D models of A549 lung cancer cells.

Synthesis, Characterization, and Anticancer Activity of Phosphanegold(i) Complexes of 3-Thiosemicarbano-butan-2-one Oxime.

Four novel phosphanegold(I) complexes of the type [Au(PR3)(DMT)].PF6 (1-4) were synthesized from 3-Thiosemicarbano-butan-2-one oxime ligand (TBO) and precursors [Au(PR3)Cl], (where R = methyl (1), ethyl (2), tert-butyl (3), and phenyl (4)). The resulting complexes were characterized by elemental analyses and melting point as well as various spectroscopic techniques, including FTIR and (1H, 13C, and 31P) NMR spectroscopy. The spectroscopic data confirmed the coordination of TBO ligands to phosphanegold(I) moiety. The solution chemistry of complexes 1-4 indicated their stability in both dimethyl sulfoxide (DMSO) and a mixture of EtOH:H2O (1:1). In vitro cytotoxicity of the complexes was evaluated relative to cisplatin using an MTT assay against three different cancer cell lines: HCT116 (human colon cancer), MDA-MB-231 (human breast cancer), and B16 (murine skin cancer). Complexes 2, 3, and 4 exhibited significant cytotoxic effects against all tested cancer cell lines and showed significantly higher activity than cisplatin. To elucidate the mechanism underlying the cytotoxic effects of the phosphanegold(I) TBO complexes, various assays were employed, including mitochondrial membrane potential, ROS production, and gene expression analyses. The data obtained suggest that complex 2 exerts potent anticancer activity against breast cancer cells (MDA-MB-231) through the induction of oxidative stress, mitochondrial dysfunction, and apoptosis. Gene expression analyses showed an increase in the activity of the proapoptotic gene caspase-3 and a reduction in the activity of the antiapoptotic gene BCL-xL, which supported the findings that apoptosis had occurred.

Antitumor potential of platinum(II) complexes of selenium donor ligands.

Platinum(II) coordination compounds are widely applied in clinics as anticancer drugs. In this review, we provide a summary of the reports on cytotoxic properties of platinum(II) complexes of selenium donor ligands along with a brief description of their structural features. It has been observed that the platinum(II) complexes of selenones and selenoethers display reasonable antitumor properties and in some cases their cytotoxic activity is greater than cisplatin. The complexes containing NH3 ligands along with selenones were found to exhibit better cytotoxicity compared to the binary Pt-selenone complexes. The mechanistic insights showed that these complexes exert antitumor activity through reactive oxygen species (ROS) generation and induction of apoptosis. The platinum-selenoether coordination compounds can self-assemble into spherical aggregates capable of self-delivery. The self-assembled Pt-selenium aggregates induce cell apoptosis via ROS, which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays.

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.

In vitro and in vivo antitumor studies of potential anticancer agents of platinum(II) complexes of dicyclopentadiene and dithiocarbamates§.

Three platinum(II) complexes of dicyclopentadiene (DCP) and dithiocarbamates (DTCs), namely, [Pt(η4-DCP)(Me2DTC)]PF6 (1), [Pt(η4-DCP)(Et2DTC)]PF6 (2), and [Pt(η4-DCP)(Bz2DTC)]PF6 (3) [Me2DTC = dimethyldithiocarbamate, Et2DTC = diethyldithiocarbamate, and Bz2DTC = dibenzyldithiocarbamate] were prepared and characterized by elemental analysis, IR, 1H, and 13C Nuclear Magnetic Resonance spectroscopy. The spectroscopic data indicated the coordination of both DCP and DTC ligands to platinum(II). The solution chemistry of complex 1 revealed that the complexes are stable in both dimethyl sulfoxide (DMSO) and 1:1 mixture of DMSO:H2O. In vitro cytotoxicity of the complexes relative to cisplatin was tested using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, against CHL-1 (human melanoma cancer cells), MDA-MB-231 (breast cancer cells), A549 (lung cancer cells), and B16 (murine melanoma cancer cells). The antiproliferative effect of all three prepared complexes was found to be significantly higher than cisplatin. Furthermore, flow cytometric analysis of complex 1 showed that the complex induced apoptosis, oxidative stress, mitochondrial potential depolarization and cell cycle arrest in a concentration-dependent pattern in the CHL-1 cells. Confirmation of apoptosis via gene expression analysis demonstrated down-regulation of anti-apoptotic genes and up-regulation of pro-apoptotic genes in the CHL-1 cells. Wound-healing assays also lent support to the strong cytotoxicity of the complexes. In vivo studies showed a significant reduction of tumor volume at the end of the experiment. In addition, the drug did not change the weight of the mice. In conclusion, complex 1 inhibited cell proliferation in vitro and reduced tumor growth in vivo.

A novel cyclic dinuclear gold(I) complex induces anticancer activity via an oxidative stress-mediated intrinsic apoptotic pathway in MDA-MB-231 cancer cells.

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1, based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopy, and X-ray crystallography. In the dinuclear complex cation [Au2(DCyPA)2]2+, the two gold(I) ions are bridged by the ligand bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) giving rise to a 16-membered ring centrosymmetric metallacycle. The cytotoxicity of the complex was evaluated against the triple-negative human breast cancer cells MDA-MB-231. In order to understand the mechanism of the cytotoxic behavior, a variety of assays, including Annexin V-FITC/Propidium iodide double staining, ROS production, and mitochondrial membrane potential and migration assays were carried out. The results indicated that complex 1 induced cytotoxicity via an oxidative stress-mediated intrinsic apoptotic pathway in MDA-MB-231 cancer cells.

Histological Changes in Renal, Hepatic and Cardiac Tissues of Wistar Rats after 6 Weeks Treatment with Bipyridine Gold (III) Complex with Dithiocarbamate Ligands.

Bipyridine gold (III) dithiocarbamate compounds are Gold-III complexes with promising cytotoxic properties. In this study, the subacute toxicity of a Gold (III) complex with dithiocarbamate ligand was evaluated. In the acute toxicity component, an initial LD50 (38.46 mg/kg) was calculated by the administration of 50, 100, 200, 400, and 800 mg/kg of the compound to five groups of rats, respectively (n = 4 each). The sixth group was the control. The sub-acute toxicity component comprised the control group A (n = 6) and the study groups B (n = 10) and C (n = 4), which were administered 1 mL distilled water, 1/10 LD50 (3.8 mg/kg), and 1/5 LD50 (7.6 mg/kg), respectively, daily for 6 weeks. The alive animals were then sacrificed. Autopsy; preservation of renal, hepatic and cardiac tissue in buffered formalin; histopathological processing; microscopic evaluation; and comparison with the controls were sequentially conducted. In the subacute toxicity study at dosages of 3.8 mg/kg and 7.6 mg/kg, the renal tubules remained unaffected with no necrosis or vacuolization. Mild to moderate renal interstitial, hepatic capsular, lobular and portal inflammation along with mild focal hepatic vacuolization were present. At 3.8 mg/kg, the cardiac muscle fibers were unremarkable in 80% (n = 8) of the specimens, with mild focal hyalinization in 20% (n = 2) of the specimens. The same was observed in 50% (n = 2) of the specimens at 7.6 mg/kg. Variable congestion was evident in all of the groups. In the subacute toxicity study, the absence of renal tubular necrosis or vacuolization, the presence of mild inflammatory hepatic and renal alterations, and predominantly unremarkable cardiac muscle fibers suggest that Bipyridine gold (III)-dithiocarbamate is safe in animal studies and is a potential candidate for clinical trials.

Anticancer Activity and Apoptosis Induction of Gold(III) Complexes Containing 2,2'-Bipyridine-3,3'-dicarboxylic Acid and Dithiocarbamates.

Three novel gold(III) complexes (1-3) of general composition [Au(Bipydc)(S2CNR2)]Cl2 (Bipydc = 2,2'-bipyridine-3,3'-dicarboxylic acid and R = methyl for dimethyldithiocarbamate (DMDTC), ethyl for diethyldithiocarbamate (DEDTC), and benzyl for dibenzyldithiocarbamate (DBDTC)) have been synthesized and characterized by elemental analysis, FTIR and NMR spectroscopic techniques. The spectral results confirmed the presence of both the Bipydc and dithiocarbamate ligands in the complexes. The in vitro cytotoxic studies demonstrated that compounds 1-3 were highly cytotoxic to A549, HeLa, MDA-231, and MCF-7 cancer cells with activities much higher (about 25-fold) than cisplatin. In order to know the possible mode of cell death complex 2, [Au(Bipydc)(DEDTC)]Cl2 was further tested for induction of apoptosis towards the MCF-7 cells. The results indicated that complex 2 induces cell death through apoptosis.

Correction to: Synthesis, spectroscopic characterization and in vitro anticancer activity of new platinum(II) complexes with some thione ligands in the presence of triethylphosphine.

Due to an unfortunate turn of events, the main affiliation of Dr. Saleh Altuwaijri was omitted from the above mentioned three articles. The complete affiliations are published below and should be treated as definitive.

Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells.

Ovarian cancer is a highly aggressive disease which is treated by surgery and platinum chemotherapy. However, a significant proportion of treated patients develop resistance to platinum treatment resulting in tumor relapse. Acquired platinum resistance has been recently correlated with activation of pro-survival endoplasmic reticulum (ER) stress responses. We hypothesized that Au complexes that induce severe ER stress might counteract pro-survival cellular attempts leading to the ER stress-mediated apoptosis and reduced platinum resistance. In this work, we prepared a series of highly cytotoxic AuI-dialkyldithiocarbamate complexes and investigated their anticancer potential in ovarian cancer cells. Complexes demonstrated surprisingly low stability in chloroform, resulting in the formation of an Au chain polymer, which also displayed excellent cytotoxicity. Lead complex 2 induced oxidative stress and ER stress-mediated p53-independent apoptosis associated with PARP cleavage and cell cycle arrest at G2/M phase. Importantly, 2 caused the surface exposure of calreticulin (CRT), which is the first step in the activation of cellular immunogenic response.

A newly synthesized platinum-based compound (PBC-II) increases chemosensitivity of HeLa ovarian cancer cells via inhibition of autophagy.

There are many mechanisms of resistance, chemoresistance of HeLa cells to anti-cancer agents seems to be autophagy-mediated. While using very effective anti-cancers such as Doxorubicin and cisplatin, cells overcome the cytotoxicity of these drugs through promotion of what so-called cytoprotective autophagy. Here in this study, we sought to introduce a novel platinum-based compound PBC-II that possesses anti-cancer activity. Our data showed that PBC-II is able to induce apoptosis at relatively low concentrations, with no detectable reactive oxygen species (ROS). However, further experiments demonstrated that exposure of HeLa cells to PBC-II did not promote autophagy; rather, it resulted in accumulation of p62 and decrease in LC3-II levels. Autophagy was then promoted in HeLa cells pharmacologically by Doxorubicin and genetically by siRNA IL-10. In order to confirm promotion of autophagy in our model, we performed acridine orange staining to assess for autophagy under microscope as well as via flow cytometry. We then measured protein level of autophagy markers p62 and LC3 by western blot. Our data indicated that PBC-II interferes with therapy-induced autophagy. We also determined PI3K activity while co-incubation of PBC-II with autophagy inducers. It was clear that PI3K activation decreased when PBC-II was co-administered with autophagy inducers. Collectively, PBC-II exerts unique anti-proliferative effects associated with inhibition of autophagy, which indicates that PBC-II is potentially a promising agent to be used in resistant ovarian tumors.

Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives.

We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1-C8) and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au2(BPM)(DMDTC)2]Cl4) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.

Periodic DFT modeling and vibrational analysis of silver(I) cyanide complexes of thioureas.

The structures of non-ionic [Ag(Tu)(CN)] (1) and ionic [Ag(Dmtu)2]+[Ag(CN)2]- (2) and [Ag(Imt)2]+[Ag(CN)2]- (3) silver(I) complexes, where Tu = thiourea, Dmtu = N,N'-dimethylthiourea and Imt = imidazoline-2-thione), were modeled by periodic DFT/PAW-PBE calculations; results were in good agreement with experiments. The bonding ability of the thiourea ligands (Tu, Dmtu and Imt) and the rival Ag-C, Ag-S, Ag-N and Ag-Ag bonds were estimated by natural population analysis and natural bonding orbital calculations. The metal-ligand bond strengths were found to decrease in the following order Ag-CCN > Ag-Sthiourea > Ag-NCN, and the main bonding contribution was covalent, donor-acceptor and electrostatic, respectively. The non-ionic [Ag(Tu)(CN)] complex formation [distinguished from the ionic Ag(I) complexes] was explained with the largest bonding capacity of the sulfur donor atom of Tu ligand and the strongest covalent and donor-acceptor Ag-S(Tu) interaction. The infrared (IR) spectra of the experimentally observed structures were reliably interpreted and the IR vibrations, which were sensitive to the ligand coordination to Ag(I) ion and to the weak intra- and intermolecular interactions, were selected with the help of DFT frequency calculations in the solid state. Graphical abstract Non-ionic and ionic complex formation and the different coordination polyhedra around Ag(I) in three AgCN complexes of thioureas were evaluated by natural population analysis, natural bonding orbital, charge density and electron localization function calculations. The predicted largest capacity of sulfur (Tu) for donor-acceptor interaction, the largest bridging sulfur ability for three Ag ions and the strongest covalent and donor-acceptor Ag-S(Tu)3 interactions in 1 as compared to 2 and 3 explain the formation of a non-ionic complex, i.e., the Ag(CN)2- anion is missing in 1.

Biological alterations in renal and hepatic tissues by a novel gold (III) anti-cancerous compound.

OBJECTIVES: Newer organo-metallic, specifically gold (III) complexes with multiple ligands are currently being formulated with primary focus of having increased anti-cancerous properties and decreased cytotoxicity. In this study, histological toxicity profile of a newly formulated anti-cancerous gold (III) compound [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) was investigated by evaluation of kidney and liver tissues of rats treated by the compound. MATERIALS AND METHODS: This is a quasi-experimental study. In acute toxicity component of the study, (n = 16) male rats weighing between 200-250 g were administered single, variable concentration of the gold (III) compound, [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) to determine LD50 (dose that is lethal to 50% of rats). An IP injection of 2.3 mg/kg (equivalent to 1/10 of LD50) was injected for 14 consecutive days to (n=10) male rats in the sub-acute component of the study. Autopsy preservation of liver and kidney tissue in buffered formalin, sample processing, histopathological evaluation, and comparison with unremarkable controls (n=5) was conducted sequentially. RESULTS: A dose of 2.3 mg/kg did not produce any tubular necrosis in kidney specimens. Mild interstitial inflammation with prominence of plasma cells was the main histological alteration. Plasmacytic pyelitis was also seen. Varying extents of cytoplasmic vacuolization and mild focal lobular and portal inflammation were predominant hepatic microscopic findings. CONCLUSION: [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) produced no histological damage in renal and hepatic tissues of rats. This very limited sample animal-based study points to the relative safety of this new gold compound. However, there is a need to compare this compound with established drugs in a comparative non-animal based study.

Gold-containing compound BDG-I inhibits the growth of A549 lung cancer cells through the deregulation of miRNA expression.

Gold complex bis(diethyldithiocarbamato-gold(I)) bis(diphenylphosphino) methane (BDG-I) is cytotoxic toward different cancer cell lines. We compared the cytotoxic effect of BDG-I with that of cisplatin in the A549 lung cancer cell line. Additionally, we investigated the molecular mechanism underlying the toxic effect of BDG-I toward the A549 cell line and the identification of cancer-related miRNAs likely to be involved in killing the lung cancer cells. Further, X-ray crystallographic data of the compound were acquired. Using microarray, global miRNA expression profiling in BDG-I-treated A549 cells revealed 64 upregulated and 86 downregulated miRNAs, which targeted 4689 and 2498 genes, respectively. Biological network connectivity of the miRNAs was significantly higher for the upregulated miRNAs than for the downregulated miRNAs. Two of the 10 most upregulated miRNAs (hsa-mir-20a-5p and hsa-mir-15b-5p) were associated with lung cancer. AmiGo2 server and Panther pathway analyses indicated significant enrichment in transcription regulation of miRNA target genes that promote intrinsic kinase-mediated signaling, TGF-ß, and GnRH signaling pathways, as well as oxidative stress responses. BDG-I crystal structure X-ray diffraction studies revealed gold-gold intramolecular interaction [Au…Au = 3.1198 (3) Å] for a single independent molecule, reported to be responsible for its activity against cancer. Our present study sheds light on the development of novel gold complex with favorable anti-cancer therapeutic functionality.

Synthesis, Characterization, and Photoelectrochemical Catalytic Studies of a Water-Stable Zinc-Based Metal-Organic Framework.

Metal-organic frameworks (MOFs) are class of porous materials that can be assembled in a modular manner by using different metal ions and organic linkers. Owing to their tunable structural properties, these materials are found to be useful for gas storage and separation technologies, as well as for catalytic applications. A cost-effective zinc-based MOF ([Zn(bpcda)(bdc)]n ) is prepared by using N,N'-bis(pyridin-4-ylmethylene)cyclohexane-1,4-diamine [N,N'-bis(pyridin-4-ylmethylene)cyclohexane-1,4-diamine] and benzenedicarboxylic acid (bdc) linkers. This new material exhibits remarkable photoelectrochemical (PEC) catalytic activity in water splitting for the evolution of oxygen. Notably, this non-noble metal-based MOF, without requiring immobilization on other supports or containing metal particles, produced a highest photocurrent density of 31 µA cm-2 at 0.9 V, with appreciable stability and negligible photocorrosion. Advantageously for the oxygen evolution process, no external reagents or sacrificial agents are required in the aqueous electrolyte solution.

Synthesis, spectroscopic characterization and in vitro anticancer activity of new platinum(II) complexes with some thione ligands in the presence of triethylphosphine.

Seven new platinum(II) complexes (1-7) of triethylphosphine (Et3P) and thiones (L) with general formula, cis-[Pt(Et3P)2(L)2]Cl2 were prepared and characterized by elemental analysis, FTIR and NMR (1H, 13C & 31P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1-6 are much better than cisplatin and carboplatin as indicated by their IC50 values.

New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status.

We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes.

Crystal structure of di-chlorido-bis-(N,N'-di-methyl-thio-urea-κS)mercury(II).

The mol-ecular structure of the title compound, [HgCl2(C3H8N2S)2], has point group symmetry 2, with the twofold rotation axis passing through the Hg(II) atom. The latter is coordinated by two Cl atoms and two N,N'-di-methyl-thio-urea (Dmtu) ligands through their S atoms, defining a distorted tetra-hedral coordination sphere with bond angles in the range 102.47 (4)-118.32 (4)°. Intra- and inter-molecular hydrogen bonds of the type N-H⋯Cl with S(6) and R 2 (2)(12) ring motifs are present. The inter-molecular contacts make up polymeric chains extending parallel to [101].