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Results for “Organogold Compounds”

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At least 19 recordsLinked to original sources
PubMed2005

Mechanisms of cytotoxicity of selected organogold(III) compounds.

The effects of a few cytotoxic organogold(III) compounds on ovarian A2780 human cancer cells were investigated in comparison to cisplatin and oxaliplatin. The tested compounds produced significant antiproliferative effects and promoted apoptosis to a greater extent than platinum drugs while causing only modest cell cycle modifications. The mechanistic implications of these findings are discussed: mitochondrial pathways are proposed to be directly involved in the apoptotic process in relation to selective inhibition of thioredoxin reductase.

Antineoplastic Agents↗
PubMed2006

Radical trapping by gold chlorides forming organogold intermediates.

Organogold compounds arising from the trapping of carbon-centered radicals by gold chlorides (AuCl, AuCl3, and HAuCl4) and colloidal gold have been characterized by different spectroscopic techniques. Laser flash photolysis has provided kinetic evidence of the occurrence of radical trapping in the microsecond time scale, while theoretical calculations give the energetics of the elementary steps. The trapping of carbon radicals by gold species observed here may explain why the presence of radical initiators enhance dramatically the activity of gold catalysts for some reactions occurring through radical intermediates.

Free Radicals↗
PubMed2004

Solution chemistry and cytotoxic properties of novel organogold(III) compounds.

The solution behaviour of some novel organogold(III) compounds was investigated, and their cytotoxic properties evaluated against a few human tumour cell lines (A2780/S, A2780/R, MCF7, HT29 and A549). Specifically, the following compounds were considered: [Au(bipy(dmb)-H)(2,6-xylidine-H)][PF(6)] (AuXyl) and [Au(bipy(dmb)-H)(p-toluidine-H)][PF(6)] (AuTol) (in which bipy(dmb)=6-(1,1-dimethylbenzyl)-2,2'-bipyridine), [Au(py(dmb)-H)(AcO)(2)] (AuPyAcO) (in which py(dmb)=2-(1,1-dimethylbenzyl)-pyridine) and [Au(pz(Ph)-H)Cl(3)]K (AuPzCl) (in which pz(Ph)=1-phenylpyrazole). The solution chemistry of these compounds, under physiological-like conditions, was investigated through UV-vis absorption and (1)H NMR spectroscopies. Significant cytotoxic effects in vitro were observed in selected cases.

Antineoplastic Agents↗
PubMed2006

Thioredoxin reductase and cancer cell growth inhibition by organogold(III) compounds.

Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon-gold bonds were evaluated for their capacity to inhibit TrxR and the growth of MCF-7 cancer cells in vitro. Compounds with up to two carbon-gold bonds were often potent inhibitors of TrxR with IC50 values as low as 2 nmol/l. In the presence of Trx and insulin the inhibiting capacity was much lower. However, the inhibitory concentrations of the compounds did not correlate with the ability to kill cells. Out of the organometallics tested, only compound 8 with two carbon-gold bonds was able to inhibit colony formation by MCF-7 breast cancer cells at low micromolar concentrations (IC50=1.6 micromol/l). Unfortunately, the compound did not show any anti-tumor activity against MCF-7 breast cancer and HT-29 colon cancer xenografts in scid mice.

Animals↗
PubMed2002

Gold(III) complexes as a new family of cytotoxic and antitumor agents.

In recent years, owing to the contributions of a few research groups, some new gold(III) compounds--either simple coordination complexes or organogold compounds--have been prepared that are sufficiently stable under physiological conditions and are promising candidates for pharmacological testing as cytotoxic and antitumor agents. In vitro pharmacological studies point out that some of these novel gold(III) complexes are highly cytotoxic toward cultured human tumor cell lines and are able to overcome resistance to platinum. Significant differences in the spectrum of action were observed compared with cisplatin. Studies are in progress to elucidate the mechanism of action of these compounds. The cellular effects of two representative gold(III) complexes are described. Preliminary results on binding to DNA in vitro are presented, pointing out that the interactions are generally weak. The implications of these results for the development of gold(III) complexes as a new family of cytotoxic and antitumor agents are discussed.

Antineoplastic Agents↗
PubMed1999

Gold(I) Compounds without Significant Aurophilic Intermolecular Interactions: Synthesis, Structure, and Electronic Properties of Ph(3)PAuC(O)NHMe and Au(3)(PhCH(2)N=COMe)(3): Comparative Monomeric and Trimeric Analogues of the Solvoluminescent Trimer, Au(3)(MeN=COMe)(3).

The preparations of Ph(3)PAuC(O)NHMe( )()and Au(3)(PhCH(2)N=COMe)(3) are reported. In solution Ph(3)PAuC(O)NHMe is unstable and readily deposits metallic gold. Colorless needles of the monomeric complex, Ph(3)PAuC(O)NHMe, crystallize in the monoclinic space group P2(1)/c, with a = 8.993(2) Å, b = 22.583(5) Å, c = 8.932(2) Å, beta = 98.22(2) degrees, at 123 K with Z = 4. Refinement of 2609 reflections and 114 parameters yielded R = 0.0455. A hydrogen-bonded intermolecular network links molecular units through N-H.O hydrogen bonds. No aurophilic interactions are present in this solid. The crystal structure of the cyclic trinuclear organogold compound, Au(3)(PhCH(2)N=COMe)(3), reveals that the complex does not associate into a trigonal prismatic array via intermolecular interactions of gold(I) centers as is seen in the triangular complex, Au(3)(MeN=COMe)(3). Rather, the complex packs in a stair-step fashion with eight discrete molecules in the asymmetric unit. Additionally, the solvent-stimulated emission (solvoluminescence) associated with Au(3)(MeN=COMe)(3) is not observed for this complex. Colorless needles of Au(3)(PhCH(2)N=COMe)(3) crystallize in the monoclinic space group P2(1), with a = 17.311(6) Å, b = 34.761(10) Å, c = 18.052(6) Å, beta = 94.73(2) degrees, at 133 K with Z = 16. Refinement of 16 250 reflections and 985 parameters yielded R = 0.0735.

Journal Article↗
PubMed1997

X-ray Crystallographic Studies of the Products of Oxidative Additions of Iodine to Cyclic Trinuclear Gold(I) Complexes: Directional Effects for Au-I.I-Au Interactions.

The crystal structures of cyclic trinuclear organogold compounds, Au(3)I(n)()(CH(3)N=COCH(3))(3) (n = 2, 4, 6) reveal that pairs of iodine atoms are added successively to each of the gold atoms in the triangular complexes. Deep red needles of Au(3)I(6)(CH(3)N=COCH(3))(3).CH(2)Cl(2) crystallize in the monoclinic space group P2(1)/c, with a = 14.762(4) Å, b = 8.723(3) Å, c = 22.278(6) Å, and beta = 91.58(2) degrees at 123 K with Z = 4. Refinement of 6591 reflections and 164 parameters yielded R = 0.055. The structure consists of columns of the molecular units united by weak iodine.iodine interactions which range in length from 3.636(2) to 3.716(2) Å. Within the molecular unit, all iodine.iodine distances are well beyond the sum of their van der Waals radii and fall in the range from 3.965(2) to 4.211(2) Å. The gold coordination is significantly distorted from planarity with I-Au-I angles of ca. 163 degrees. In Au(3)I(6)(CH(3)N=COCH(3))(3) the intermolecular I.I interactions are significantly shorter than the intramolecular I.I contacts. Red parallelepipeds of the tetraiodo complex, Au(2)I(4)Au(CH(3)N=COCH(3))(3), crystallize in the triclinic space group P&onemacr;, with a = 7.404(2) Å, b = 9.278(2) Å, c = 16.331(3) Å, alpha = 80.77(3) degrees, beta = 78.68(3) degrees, and gamma = 81.85(3) degrees at 123 K with Z = 2. Refinement of 4963 reflections and 124 parameters yielded R = 0.048. No noteworthy intermolecular contacts are present in this compound. Orange-red hexagonal plates of the diiodo complex, AuI(2)Au(2)(CH(3)N=COCH(3))(3), crystallize in the monoclinic space group P2(1)/c, with a = 9.309(4) Å, b = 13.597(4) Å, c = 14.899(5) Å, and beta = 101.26(3) degrees at 123 K with Z = 4. Refinement of 4133 reflections and 121 parameters yielded R = 0.064. This structure consists of discrete molecular units displaying no noteworthy inter- or intramolecular contacts.

Journal Article↗
PubMed2004

Toward a novel metal-based chemotherapy against tropical diseases. 7. Synthesis and in vitro antimalarial activity of new gold-chloroquine complexes.

A number of new Au(I) and Au(III) complexes of chloroquine (CQ) have been prepared, characterized, and evaluated in vitro against several strains of Plasmodium falciparum. [(CQ)Au(PPh(3))][NO(3)] (2) was synthesized by reaction of AuCl(PPh(3)) with AgNO(3) followed by treatment with CQ. Similar reactions of AuCl(PR(3)) (R = Me, Et) with KPF(6) and CQ yielded [(CQ)Au(PMe(3))][PF(6)] (3), and [(CQ)Au(PEt(3))][PF(6)] (4), respectively. KAuCl(4) reacted with CQ to produce the Au(III) complex [(CQ)(2)Au(Cl)(2)]Cl (5), which in turn formed [(CQ)Au(Cl)(SR)(Et(2)O)]Cl (6) by reaction with 1-thio-beta-d-glucose-2,3,4,6-tetraacetate (SRH). The new compounds were characterized by a combination of elemental analysis, fast atom bombardment mass spectrometry (FAB-MS), and NMR spectroscopy. All the complexes display in vitro activity against CQ-sensitive and CQ-resistant strains of Plasmodium falciparum. The highest activity for this series was obtained for complex 4, which is 5 times more active than chloroquine diphosphate (CQDP) against the CQ-resistant strain FcB1. On preincubation of noninfected red blood cells with complexes 1, 5, and 6, protection against subsequent infection was observed in some cases. No clear structure-activity correlations could be established for this series of compounds.

Animals↗
PubMed2006

A mass spectrometric investigation of the binding of gold antiarthritic agents and the metabolite [Au(CN)2]- to human serum albumin.

Electrospray ionisation (ESI) mass spectrometry was used to examine the reactions of the clinically used antiarthritic agent [Au(S2O3)2]3-, and AuPEt3Cl, a derivative of another clinically used agent auranofin, with human serum albumin (HSA) obtained from a human volunteer. Both compounds reacted readily with HSA to form complexes containing one or more covalently attached gold fragments. In the case of AuPEt3Cl, binding was accompanied by the loss of the chloride ligand, while for [Au(S2O3)2]3- the mass spectral data indicated binding of Au(S2O3) groups. Experiments performed using HSA with Cys34 blocked by reaction with iodoacetamide were consistent with reaction of both gold compounds with this amino acid. Separate blocking experiments using diethylpyrocarbonate and AuPEt3Cl also provided evidence for histidine residues acting as lower-affinity binding sites for this gold compound. ESI mass spectra of solutions containing [Au(S2O3)2]3- or [Au(CN)2]-, and HSA, provided evidence for the formation of protein complexes in which intact gold molecules were non-covalently bound. In the case of [Au(S2O3)2]3-, these non-covalent complexes proved to be transitory in nature. However, for [Au(CN)2]- a non-covalent complex containing a single gold molecule bound to HSA was found to be stable, and constituted the main adduct formed in solutions containing low-to-medium Au-to-HSA ratios. Evidence was also obtained for the formation of a covalent adduct in which a single Au(CN) moiety was bonded to Cys34 of the protein. AuPEt3Cl reacted to a much lower extent with HSA that had Cys34 modified by formation of a disulfide bond to added cysteine, than with unmodified HSA. This suggests that the extent of modification of the protein in vivo may have an important influence on the transport and bioavailability of gold antiarthritic drugs.

Antirheumatic Agents↗
PubMed2003

Preclinical tolerance and pharmacokinetic assessment of MU-Gold, a novel chemotherapeutic agent, in laboratory dogs.

MU-Gold, tetrakis (trishydroxymethyl) phosphine gold(I) chloride, a novel gold compound, has cytotoxic effects against human androgen-dependent and -independent prostatic, gastric, and colonic carcinoma in cell culture and against malignant lymphoma in rodent models. A pilot study was conducted to evaluate the tolerance and pharmacokinetic properties of MU-Gold in normal dogs in anticipation of clinical trials in cancer-bearing dogs. MU-Gold (10 mg/kg) was administered by i.v. injection to three purpose-bred dogs. Serum was collected from all dogs for measurement of gold levels via atomic absorption spectrometry. In addition, complete blood counts and biochemical profiles were monitored for Dogs 2 and 3 every 7 days for 30 days. A two-compartment i.v. bolus model with first-order kinetics, mean elimination half-life of approximately 40 hours, and mean volume of distribution of 0.6 L/kg was established. Serum gold concentrations ranging from 10 to 50 mcg/ml were sustained for 2 to 3 days with no clinically significant toxicities observed. Based on in vitro results in earlier studies and preliminary pharmacokinetic data collected in the present study, Phase I clinical trials should be conducted to define the optimal dosage, dose-limiting toxicities, and other characteristics of MU-Gold that will be used to design Phase II clinical trials.

Animals↗
PubMed1989

Cholestasis and pneumonitis induced by gold therapy.

The authors describe the association of gold salt-induced cholestasis and lymphocytic alveolitis proved by liver biopsy and broncho-alveolar lavage. To our knowledge this is the third case report on the combination of liver disease and pulmonary infiltration induced by gold compounds.

Aged↗
PubMed2004

Acyl coenzyme A:cholesterol acyltransferase inhibitors as hypolipidemic and antiatherosclerotic drugs.

Acyl coenzyme A:cholesterol acyltransferase (ACAT) is the enzyme that catalyzes the conversion of intracellular cholesterol into cholesteryl esters. Two ACAT isoforms, termed ACAT1 and ACAT2, have been described. ACAT1 is ubiquitously found, with high expression levels in macrophages, adrenals, sebaceous glands and foam cells from human atherosclerotic lesions. In contrast, ACAT2 expression is restricted to the intestine and the liver of mice and non-human primates. The reaction catalyzed by ACAT is essential for intestinal cholesterol absorption, synthesis and secretion of apolipoprotein B (apoB)-containing lipoproteins, and intracellular storage of cholesterol. Therefore, ACAT inhibitors would theoretically reduce plasma cholesterol levels by blocking cholesterol absorption from the diet and by reducing hepatic VLDL synthesis. Moreover, ACAT inhibition could limit the accumulation of cholesteryl esters in the cytoplasm of macrophages, thus reducing the formation of foam cells. In view of these attractive possibilities, a great deal of molecules with ACAT inhibitory properties have been synthesized in the last 20 years. However, only a few of them have reached clinical studies, mainly due to unexpected side effects. On the other hand, most of the compounds assayed in humans have not shown substantial hypolipidemic efficacy. The present article focuses on the current knowledge of the pharmacology of ACAT inhibitors, and, specifically, on the different pharmacological approaches used to evaluate these compounds as hypolipidemic and antiatherosclerotic agents.

Animals↗