Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THIOSEMICARBAZONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed2006

Development and validation of HPLC-DAD methods for the analysis of two novel iron chelators with potent anti-cancer activity.

Di-2-pyridylketone isonicotinoyl hydrazone (PKIH) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) novel iron chelators which possess marked anti-cancer activity in vivo. However, further progress in the development of these drug candidates requires precise and convenient methods for their qualitative and quantitative analysis. The aim of this study was to develop and validate HPLC methods suitable for the purity and stability evaluation of Dp44mT and PKIH and subsequently to employ these methods in stress tests addressing their chemical stability. The chromatographic analyses of both chelators were accomplished via HPLC using a Discovery HSF5 column (25 cm x 4 mm; 5 microm). For separation of Dp44mT and its synthetic precursors, the mobile phase was composed of a mixture of 2 mM EDTA and acetonitrile in a ratio 60:40 (v/v). A desirable separation of PKIH from its synthetic precursors was achieved with a mixture of 0.01 M phosphate buffer (pH 3.0), methanol and acetonitrile in a ratio of 65:21:14 (v/v/v) with the addition of EDTA (2 mM). In order to confirm the utility of these HPLC methods for measuring these drugs and their stability, Dp44mT and PKIH were subjected to chemical stress tests. These experiments showed that Dp44mT was relatively stable against hydrolytic degradation, but quite sensitive to oxidation. On the other hand, PKIH was slightly sensitive to acid-catalyzed hydrolysis, but it was relatively stable under other tested conditions. Furthermore, these studies confirmed the utility of these methods not only for appropriate evaluation of purity but also stability. The analytical methods developed and validated in this study, as well as the basic data on the chemical stability, should further support the development of both these novel anti-cancer chelators as promising drug candidates.

Antineoplastic Agents↗
PubMed2003

Preparation of 2,6-anhydro-aldose acylhydrazones, -semicarbazones and -oximes from 2,6-anhydro-aldononitriles (glycosyl cyanides).

Reductive transformation of per-O-acylated 2,6-anhydro-aldononitriles (glycopyranosyl cyanides of the D-galacto, D-gluco, D-xylo, and D-arabino configuration) with Raney-nickel-NaH(2)PO(2) in pyridine-AcOH-water solvent mixture in the presence of benzoylhydrazine, ethyl carbazate, and semicarbazide gave the corresponding anhydro-aldose benzoylhydrazones, -ethoxycarbonylhydrazones, and -semicarbazones, respectively. Acid catalyzed transimination of the semicarbazones with thiosemicarbazide, hydroxylamine, and O-benzylhydroxylamine, resulted in the formation of anhydro-aldose thiosemicarbazones, and E/Z mixtures of anhydro-aldose oximes, and O-benzyl-(anhydro-aldose)-oximes, respectively.

Acids↗
PubMed1999

Synthesis, structure, spectroscopic properties and biological activity of mixed diorganotin(IV) complexes containing pyridine-2-carbaldehyde thiosemicarbazonato and diphenyldithiophosphinato ligands.

Reaction of the title ligands (HPyTSC and HS(S)PPh2, respectively) with R2SnO (R = Me, Et, Bu) in ethanol (EtOH) afforded the complexes [SnMe2(PyTSC) (S2PPh2)].EtOH (1) and [SnR2(PyTSC) (S2PPh2)] (R = Et (2), Bu (3)). The structures of 1 and 2 were determined by single-crystal X-ray diffractometry. In both these complexes the tin atom is coordinated to an N,N,S-dentate thiosemicarbazonate ligand, an anisobidentate dithiophosphinato ligand and the two R groups. The coordination polyhedrons can be described as distorted pentagonal bipyramids. A comparative study of the IR spectra of 1, 2 and 3 indicates that the butyl complex has a similar structure. Multinuclear (1H, 13C, 31P and 119Sn) NMR data suggest that the structures of 1 and 2 probably remain in CDCl3 (or DMSO-d6) solution but compound 3 partially decomposes in these media. Preliminary results on the effects of the complexes on the proliferation and differentiation of FLC, CEM, U937, K562 and TOM-1 leukaemia cells, and on the clonogenic activity of K562 cells are also described.

Cell Differentiation↗
PubMed2003

Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.

The era of antiviral chemotherapy started more than 50 years with the findings by Domagk and his colleagues that thiosemicarbazones showed activity against vaccinia virus. One of the derivatives, methisazone, was even investigated in the prophylaxis of smallpox. With the successful implementation of the smallpox vaccine, the use of methisazone was not further pursued. Should there be a threat of smallpox or other poxvirus infections, that could not be immediately controlled by vaccination, a therapeutic intervention could be envisaged based on several therapeutic strategies targeted at such cellular enzymes as IMP dehydrogenase, SAH hydrolase, OMP decarboxylase and CTP synthetase, as well as viral enzymes such as the DNA polymerase. Most advanced as a therapeutic or early prophylactic modality to tackle poxvirus infection is cidofovir, which was found active (i) in vitro against all poxviruses studied so far; (ii) in vivo, against vaccinia and cowpox virus infections in experimental animal models; as well as (iii) some human poxvirus infections, such as molluscum contagiosum. In case of an inadvertent poxvirus epidemic, antiviral therapy (i.e. with cidofovir) will offer the possibility to provide short-term prophylaxis, or therapy. Cidofovir should also allow to treat severe complications of vaccination as may happen in for example immunosuppressed patients.

Animals↗
PubMed2003

In vitro induction of fetal hemoglobin in human erythroid progenitor cells.

OBJECTIVE: Clinical heterogeneity among patients with sickle cell anemia (SCA) is influenced by the amount of fetal hemoglobin (HbF) within circulating erythrocytes. Current pharmacotherapy focuses on increasing HbF in order to reduce hemolysis and help prevent acute vaso-occlusive events. Hydroxyurea, a known S-phase-specific cytotoxic ribonucleotide reductase (RR) inhibitor, is an effective agent for HbF induction in patients with SCA, but the mechanisms by which hydroxyurea induces HbF in vivo have not been elucidated. MATERIALS AND METHODS: We adapted an in vitro assay for HbF induction, growing burst-forming unit erythroid (BFU-E) colonies in methylcellulose from peripheral blood of children with SCA and extracting the hemoglobin for high-performance liquid chromatography analysis of HbF. Hydroxyurea and other known RR inhibitors, along with cytotoxic agents that are not RR inhibitors, were tested for the ability to induce HbF using this in vitro assay. RESULTS: Hydroxyurea decreased the number of BFU-E colonies that grew in culture and significantly increased HbF from 13.6%+/-6.2% to 25.4%+/-8.0% at 50 microM HU (p=0.012). Three other known RR inhibitors also significantly induced HbF: 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (p=0.025), guanazole (p=0.008), and gemcitabine (p=0.028). Cytarabine and alkylating agents BCNU and 4-hydroperoxycyclophosphamide, which are cytotoxic agents but not RR inhibitors, reduced BFU-E colony number but did not significantly induce HbF. CONCLUSION: Hydroxyurea and other RR inhibitors significantly induce HbF in vitro in human erythroid progenitor cells. Inhibition of RR may be a critical mechanism by which hydroxyurea increases HbF in vivo in patients with SCA.

Anemia, Sickle Cell↗
PubMed2002

A novel type of nonsteroidal estrone sulfatase inhibitors.

Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil bacterium Nonomuria rubra and belongs to the family of benzo[a]naphthacenequinones. We report the initial results and structure-activity relationships of our study into a series of thiosemicarbazone derivatives of madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone sulfatase. The most active compound, the cyclohexylthiosemicarbazone, was shown to be a non-competitive inhibitor with a K(i) of 0.35microM. This compound is devoid of estrogenic properties and showed low acute toxicity in the hen's fertile egg screening test.

Cytosine↗
PubMed2002

Iron chelators as therapeutic agents for the treatment of cancer.

A wide variety of studies in vitro, in vivo, and in clinical trials have demonstrated that the chelator currently used to treat iron overload disease, desferrioxamine, has anti-proliferative effects against both leukemia and neuroblastoma. However, the efficacy of desferrioxamine is severely limited due to its poor ability to permeate cell membranes and chelate intracellular iron pools. These studies have led to the development of other iron chelators that are far more effective than desferrioxamine. Some of these chelators such as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) have entered phase I clinical trials, while other chelators such as 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone or tachpyridine require evaluation in animal models. The high anti-tumor activity observed with these ligands certainly suggests further development of chelators as anti-cancer agents is warranted.

Animals↗
PubMed2004

EPR, magnetic and spectral studies of copper(II) and nickel(II) complexes of schiff base macrocyclic ligand derived from thiosemicarbazide and glyoxal.

A new macrocylic Schiff base 1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione-2,4,8,10-tetraene(H(2)L(4)) containing thiosemicarbazone moiety is readily prepared and characterized for the first time with fairly good yield. Macrocylic ligand (H(2)L(4)) is prepared from the mesocyle 6-ethoxy-4-thio-2,3,5-triazine(H(2)L(3)) in ethanol with copper chloride acting as template using high dilution technique. The complexes of macrocylic ligand with a general composition M(H(2)L(4))X(2) [where M=Cu(II) or Ni(II); H(2)L(4)=1,2,5,6,8,11-hexaazacyclo dodeca-7,12-dithione-2,4,8,10-tetraene; X= Cl(-), NO(3)(-), (1)/(2)SO(4)(2-)] and ML(4) (where metal salt used to synthesize complex is copper acetate and nickel thiocyanate) have been synthesized. The complexes were characterized on the basis of elemental analysis, molar conductance, magnetic susceptibility, IR, electronic, 1H NMR, mass and EPR spectral studies. The complexes from H(2)L(4) show different stoichiometry ratio and with a variable grade of deprotonation in the ligand, depending upon the salt used and working conditions.

Copper↗
PubMed1995

Non-sialate inhibitor of influenza A/WSN/33 neuraminidase.

An N1 strain of influenza A virus neuraminidase (A/WSN/33 NA) was purified and used to screen for inhibitors. As a result, a well-known tuberculostatic, 4'-formylacetanilide thiosemicarbazone (or thiacetazone), was identified. Thiacetazone is a non-sialate compound and inhibits the enzyme in a noncompetitive manner with respect to the substrate sialic acid. Mechanistic studies indicate that the inhibition was due to the competition of thiacetazone with Ca2+, which maintains N1 neuraminidase in an active conformation. The Ki for the inhibition was estimated to be about 4 microM. Equilibrium exchange experiments revealed that when purified A/WSN/33 NA was incubated with 5 microM 45CaCl2, 2 mol of 45Ca2+ ion was exchanged into each mole of NA tetramer and subsequently displaced from the enzyme upon the introduction of the inhibitor. Inhibition of plaque formation by thiacetazone in an MDCK cell culture that had been infected with the influenza A/WSN/33 virus was demonstrated. Thiacetazone was highly specific for A/WSN/33 neuraminidase, since little effect was noted when it was tested against NAs from the other strains of influenza virus or from bacteria. This compound might represent a group of non-sialate inhibitors of influenza NA that bind to a noncatalytic or an allosteric site on the enzyme.

Animals↗
PubMed2003

Hypoxia-targeting copper bis(selenosemicarbazone) complexes: comparison with their sulfur analogues.

The first copper bis(selenosemicarbazone) complexes have been synthesized, using the ligands glyoxal bis(selenosemicarbazone), pyruvaldehyde bis(selenosemicarbazone), and 2,3-butanedione bis(selenosemicarbazone). Their spectroscopic properties indicate that they are structurally analogous to their well-known square-planar sulfur-containing counterparts, the copper bis(thiosemicarbazone) complexes. Spectroscopic comparison of the sulfur- and selenium-containing complexes provides insight into their electronic structure. The effects on spectroscopic and redox properties of replacing sulfur with selenium, and of successive addition of methyl groups to the ligand backbone, are rationalized in terms of their electronic structure using spin-unrestricted density functional calculations. These suggest that, like the sulfur analogues, the complexes have a very low-lying empty ligand-based pi-orbital immediately above the LUMO, while the LUMO itself has d(x2)-(y2) character (i.e., is the spin partner of the HOMO). Replacement of S by Se shifts the oxidation potentials much more than the reduction potentials, whereas alkylation of the ligand backbone shifts the reduction potentials more than the oxidation potentials. This suggests that oxidation and reduction involve spatially different orbitals, with the additional electron in the reduced species occupying the ligand-based pi-orbital rather than d(x2)-(y2). Density functional calculations on the putative singlet Cu(I)-reduced species suggest that this ligand pi-character could be brought about by distortion away from planarity during reduction, allowing the low-lying ligand pi-LUMO to mix into the d(x2)-(y2)-based HOMO. The analogy in the structure and reduction behavior between the sulfur- and selenium-containing complexes suggests that labeled with positron emitting isotopes of copper (Cu-60, Cu-62, Cu-64), the complexes warrant biological evaluation as radiopharmaceuticals for imaging of tissue perfusion and hypoxia.

Copper↗
PubMed1985

Optimization of the Schiff bases of N-hydroxy-N'-aminoguanidine as anticancer and antiviral agents.

Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-hydroxy-N'-aminoguanidine. Synthesis and structure-activity studies of some of these compounds point to increased size and lipophilicity as important factors for activity. To optimize the activities of this series of compounds, 13 derivatives of high lipophilicity and molecular size have been synthesized and their biological activities studied. The most active anticancer compounds against L1210 in vitro (compounds 9 and 12) are about 7 times more active than hydroxyguanidine and hydroxyurea. The most active antiviral compounds against Rous sarcoma virus transformation of chick fibroblasts in vitro (7, 9) are about 40 times more active than hydroxyguanidine. One of the compounds (4) shows promising activity in vivo (% T/C = 140 against P388 leukemia in mice) and is undergoing further studies by the National Cancer Institute (NCI). Studies of the inhibition of transformation of chick embryo cells by Rous sarcoma virus show that all these compounds inhibit transformation while some compounds inhibit viral replication as well.

Animals↗
PubMed1977

Potential steroidal antiestrogens.

A series of analogues of 17beta-estradiol has been synthesized and the compounds have been tested, using sucrose density gradient analysis, for their ability to compete with [6,7-3H]-17beta-estradiol for the estrogen-receptor protein from mouse uterine homogenates. Active compounds were also tested for antiuterotrophic activity in immature rats and/or mice. 3,17beta-Dihydroxy-6-phenylestra-1,3,5(10),6-tetraene (14) was the most active new compound in the in vitro test suppressing the binding of 17beta-estradiol by 34 and 87%, respectively, at molar ratios of 1 and 3.16. It was significantly more potent than the intermediate 6-oxoestradiol (4) which produced a 52% inhibition of binding at a molar ratio of 3.16. The thiosemicarbazone of 6-oxoestradiol (17) and the derived 3,17beta-dihydroxy-6-(2-imino-4-oxothiazolidinyl-1-imino)estra-1,3,5(10)-triene (19) produced, respectively, only 46 and 16% inhibition of binding at a molar ratio of 10. Introduction of a 1-methyl substituent into either 6-oxo or 6-phenyl compounds reduced affinity for the receptor significantly (compounds 5 and 15) and conversion of the 3-OH into a beta-dialkylaminoethoxy group virtually destroyed all binding activity (compounds 2, 6, 10, and 11). At a molar ratio of 10 compound 14 failed to suppress the uterine weight response of immature rats to 17beta-estradiol, whereas compound 15, at a molar ratio of 200, produced a significant increase in the uterine weight of immature rats but not of immature mice even at a molar ratio of 1000.

Animals↗
PubMed1976

Antineoplastic and biochemical properties of arylsulfonylhydrazones of 2-formylpyridine N-oxide.

The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2-formylpyridine N-oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene, quinoline, or isoquinoline resulted in loss of activity (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N-oxide produced inactive agents (c) the pyridine N-oxide function was essential for anticancer activity, except for 4-substituted derivatives which were active without the N-oxide group, (d) replacement of the SO2 group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO2 and aryl ring with retention of anticancer potency. One of the most active members of this series, 1-oxidopyridine-2-carboxaldehyde p-toluenesulfonylhdrazone, exhibited antineoplastic activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine-3H and uridine-3H incorporation into DNA and RNA, respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound.

Animals↗
PubMed1976

Phosphorus-nitrogen compounds. 20. Thiophosphorus hydrazones.

Six pyridine-2-carboxaldehyde, one pyridine N-oxide 2-carboxaldehyde, and five diketone thiophosphoric hydrazones, three thiophosphoric hydrazides, and two cupric chelates were synthesized. The chelates and nine of the hydrazones were tested against Ehrlich ascites carcinoma. Seven of these latter agents were administered concurrently with either cupric and/or ferrous salts to mice bearing this tumor. The greatest activity was found with the chelate, cimethyl pyridine-2-carboxyaldehyde phosphorothioic hydrazone-copper (1:1). The hydrazone portion of this chelate also formed a ligand-copper (2:1) complex. Although all of the hydrazones but one were inactive when evaluated alone, the concurrent injection of cupric ion increased survival times by an avoli alkaline phosphatase was found to be inhibited by two thiosemicarbazones in a manner similar to that previously reported by these agents against alkaline phosphatase derived from Sarcoma 180-6-thiopurine resistant ascites cells. None of the 14 hydrazides or hydrazones tested against E. coli enzyme displayed significant inhibition.

Alkaline Phosphatase↗
PubMed2006

Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells.

We report the synthesis of novel 1:1 Schiff base copper complexes of quinoline-2-carboxaldehyde showing dose-dependent, antiproliferative, and proapoptotic activity in PC-3 and LNCaP prostate cancer cells. We found that quinoline thiosemicarbazone 2 (FPA-137) was the most potent and inhibited proteosome activity in intact human prostate cancer PC-3 and LNCaP cells (IC50 of 4 and 3.2 microM, respectively) compared to clioquinol and pyrrolidine dithiocarbamate (IC50 of 10 and 20 microM), supporting the novelty of 2.

Aldehydes↗
PubMed1990

Are reduction potentials of antifungal agents relevant to activity?

Cyclic voltammetry data were obtained for several categories of fungicidal agents including quinones (akrobomycin, podosporin A), iminium ions and precursors (pyridazines, 15-azahomosterol, griseofulvin-4'-oxime), and metal derivatives of chelators (pyridine-2-aldehyde thiosemicarbazones). The reductions usually occurred in the range of -0.7 to +0.3 V. Reduction potentials provide information on the feasibility of electron transfer in vivo. Catalytic production of oxidative stress from redox cycling is a possible mode of action. Alternatively, there may be interference with normal electron transport chains.

Antifungal Agents↗
PubMedDate not supplied

[Synthesis from tigogenin and antituberculosis activity of some of the derivatives of 5alpha-ketosteroid hydrazones].

Isonicotinoylhydrazones and thiosemicarbazones of some 5alpha-ketosteroids were synthesized from tigogenin, and their structures were confirmed by NMR and IR spectroscopy and mass spectrometry. Their antimycobacterial activities were studied, and it was shown that some of the synthesized isonicotinoylhydrazones exhibit a high antituberculosis activity. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

Antitubercular Agents↗
PubMed1991

Indirect determination of free cyanide in industrial waste effluent by atomic absorption spectrometry.

An indirect method is described for the determination of free cyanide in industrial waste effluent samples by atomic absorption spectrometry (AAS). In an alkaline medium, cyanide forms a stable complex species [Cu(BPTC)(CN)] (BPTC = 2-benzoylpyridine thiosemicarbazone), which can be extracted into a mixture of isobutyl methyl ketone-isopentyl alcohol (7 + 1) with an efficiency of greater than 98.5%. The extract can be analysed directly for copper (and hence indirectly for cyanide) by flame AAS. The calibration graph is linear up to 5.7 micrograms of cyanide per millilitre of solvent mixture and the limit of detection is 4.8 ng ml-1. A large number of foreign ions were found not to interfere with the proposed method.

Cyanides↗