SEARCH · PubMed Health

Results for “THIOSEMICARBAZONES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 55 records · Page 3Linked to original sources

PubMed1976

Potential antitumor agents. 14. 4-Substituted 2-formylpyridine thiosemicarbazones.

A series of 4-substituted 2-formylpyridine thiosemicarbazones has been synthesized which contain a tertiary N at the 4 position. These materials were obtained by reacting 4-nitro-2-picoline N-oxide, either directly or after conversion to the corresponding 4-chloro derivative, with a variety of secondary amines. Rearrangement of the 4-substituted 2-picoline N-oxides with Ac2O yielded respective methyl acetates, which upon acid hydrolysis, MnO2 oxidation, and reaction with thiosemicarbazide resulted in the desired compounds. An alternate procedure which consisted of reacting 4-chloro-2-formylpyridine ethylene acetal with various amines, followed by hydrolysis and reaction with thiosemicarbazide, was also employed. Introduction of an alkyl group at the 3 position of the pyridine ring of 4-morpholino-2-formylpyridine thiosemicarbazone was achieved by utilizing 2,3-dimethyl-4-nitropyridine N-oxide; this material was converted to the corresponding 4-chloro derivative which was then subjected to nucleophilic substitution. 4-Morpholino-2-formylpyridine thiosemicarbazone was the most active antineoplastic agent of this series in mice bearing Sarcoma 180 ascites cells and was significantly superior to 5-hydroxy-2-formylpyridine thiosemicarbazone in this test system.

Animals↗

PubMed1996

Synthesis and biological activity of 3- and 5-amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone.

A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogues of pyridine-2-carboxaldehyde thiosemicarbazone, have been synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Alkylation of 3- and 5-amino-2-(1,3-dioxolan-2-yl)pyridines (1, 2) resulted in corresponding 3-methylamino, 5-methylamino, 3-allylamino, 5-ethylamino, 5-allylamino, 5-propylamino, and 5-butylamino derivatives (5, 6, and 11-15), which were then condensed with thiosemicarbazide to yield the respective thiosemicarbazones (7, 8, and 16-20). Oxidation of 3,5-dinitro-2-methylpyridine (21) with selenium dioxide, followed by treatment with ethylene glycol and p-toluenesulfonic acid, produced the cyclic ethylene acetal, 23. Oxidation of 2-(1,3-dioxolan-2-yl)-4-methyl-5-nitropyridine (26) with selenium dioxide, followed by sequential treatment with sodium borohydride, methanesulfonyl chloride, and morpholine afforded the morpholinomethyl derivative 30. Catalytic hydrogenation of 23 and 30 with Pd/C yielded the corresponding amino derivatives 24 and 31. Catalytic hydrogenation of 5-cyano-2-methylpyridine (33) with Raney nickel, followed by treatment with acetic anhydride, gave the amide derivative 35. N-Oxidation of 35, followed by rearrangement with acetic anhydride, produced the acetate derivative, 5-[(acetylamino)methyl]-2-(acetoxymethyl)pyridine (37). Repetition of the N-oxidation and rearrangement procedures with compound 37 yielded the diacetate derivative 39. Condensation of compounds 24, 31, and 39 with thiosemicarbazide afforded the respective 3,5-diaminopyridine-, 4-(4-morpholinylmethyl)-5-aminopyridine-, and 5-(aminomethyl)pyridine-2-carboxaldehyde thiosemicarbazones (25, 32, and 40). The most biologically active compounds synthesized were the 5-(methylamino)-, 5-(ethylamino)-, and 5-(allylamino)pyridine-2-carboxaldehyde thiosemicarbazones (8, 17, and 18), which were potent inhibitors of ribonucleotide reductase activity with corresponding IC50 values of 1.3, 1.0, and 1.4 microM and which produced significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 being obtained when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, respectively.

Animals↗

PubMed1973

Inhibition of RNA-dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations.

The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin beta-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity. Two cations, Cu(++) and Hg(++), can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism between N-methyl isatin beta-thiosemicarbazone and Cu(++) occurs, since treatment of the virus with a low dose of either N-methyl isatin beta-thiosemicarbazone or Cu(++) has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions. Several cations (Ag(+), Co(++), Zn(++), Cd(++), and Ni(++)) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.

Animals↗

PubMed1986

Structure-activity relationships among alpha-(N)-heterocyclic acyl thiosemicarbazones and related compounds as inhibitors of herpes simplex virus type 1-specified ribonucleoside diphosphate reductase.

2-Acetylpyridine thiosemicarbazone, a potent antiviral drug, and 13 analogues were examined as inhibitors of partially purified herpes simplex virus type 1-specified ribonucleoside diphosphate reductase. N4,N4-Azacycloheptane derivatives were more active than their N4-unsubstituted analogues. Selenosemicarbazones were similar in potency to their thiosemicarbazone congeners, whereas a related semicarbazone was much less active. Maximum inhibition was observed when an ethylidene side-chain was present in the compounds. No discernible trend in potency was observed when the pyridine moiety was replaced by quinoline or isoquinoline. Thiosemicarbazide derivatives were less potent than their unsaturated thiosemicarbazone analogues. Inhibitory potencies increased at longer incubation times consistent with the hypothesis that thiosemicarbazones inactivate the enzyme in a time-dependent manner.

Ribonucleoside Diphosphate Reductase↗

PubMed1988

Induction of process outgrowth in vertebrate and invertebrate cell lines by a 2-pyridinyl thiosemicarbazone.

Regulation of differentiation in cells of disparate origin is often mediated by widely differing molecular signals and receptor mechanisms. For example, two neuron-like cell lines used extensively as models for molecular control of differentiation, the steroid-sensitive Kc line from Drosophila and the polypeptide- and cyclic nucleotide-sensitive PC12 line from rat, share no obvious growth factor or hormone receptors. However, we have found that a thiosemicarbazone, 1-pyrrolidinecarbothioic acid [1-(2-pyridinyl)ethylidene] hydrazide, one of a class of synthetic antineoplastic agents, induces process outgrowth - a marker of cellular differentiation - in cells of both of these lines. Moreover, the thiosemicarbazone induces process outgrowth in cells of mutant clones of these lines that are refractory to treatment with growth factors or hormones. Activity of the thiosemicarbazone is dependent upon the alpha-(N)-heterocyclic ring. These findings show that the 2-pyridinyl thiosemicarbazone mimics the effects of diverse epigenetic factors in inducing process outgrowth similar to that seen in cellular differentiation of these cell lines induced by natural regulators. Regulation may be by a mechanism, common to both invertebrate and vertebrate cells, which occurs downstream from the receptors that have been previously shown to mediate epigenetically induced differentiation.

Animals↗

PubMed1975

Isolation and characterization of a gamma-thiochromanone-4-thiosemicarbazone-resistant mutant of vaccinia virus.

gamma-Thiochromanone-4-thiosemicarbazone (TCT) inhibits the growth of vaccinia virus in BSCl cells by interfering with viral maturation. A mutant of the virus (TCT(R)) which is resistant to this drug was isolated. This mutant also exhibits resistance to another thiosemicarbazone related compound, isatin beta-thiosemicarbazone (IBT). There is a good correlation between the cross-resistance of the two mutants IBT(R) and TCT(R) to TCT and IBT, respectively, and the similar antipoxvirus activity of these two thiosemicarbazone-related compounds.

Benzopyrans↗

PubMed1968

Sensitivity of herpes simplex virus, vaccinia virus, and adenoviruses to deoxyribonucleic acid inhibitors and thiosemicarbazones in a plaque suppression test.

Herpes simplex and vaccinia viruses and adenovirus types 1, 2, 5, and 7 were tested by plaque suppression methods for sensitivity to halogenated deoxyuridines (5-iodo-, 5-bromo-, 5-chloro-, and 5-fluoro-), cytosine arabinoside, isatin-beta-thiosemicarbazone, and N-methylisatin-beta-thiosemicarbazone. After incubation for 12 days in HeLa cell cultures, vaccinia virus plaques were still readily suppressed by deoxyribonucleic acid (DNA) inhibitors and thiosemicarbazones. Herpes simplex virus plaques were likewise suppressed by at least three DNA inhibitors. Adenovirus plaques were not suppressed by DNA inhibitors or thiosemicarbazones. 5-Fluoro-2'-deoxyuridine could not be shown to have any antiviral activity, but it did produce a substantial lethal action on the cells.

Adenoviridae↗

PubMed2003

Inhibitory effect of thiosemicarbazone derivatives on Junin virus replication in vitro.

The inhibitory effect of several thiosemicarbazones (TSCs), synthesized from aromatic ketones and terpenones, and their heterocyclic thiadiazoline (TDZ) derivatives, was investigated against Junin virus (JUNV), an arenavirus agent of Argentine haemorrhagic fever. From the 25 compounds tested, six compounds belonging to the TSC group were found to be selective inhibitors of JUNV, with EC50 values determined by a virus yield inhibition assay in the range 3.4-12.5 microM, and selectivity indices greater than 10. By contrast, most of the TDZs obtained by heterocyclization of the TSCs were not active against JUNV. No conclusive structure-activity relationships could be established but systematically higher activity was associated to TSCs derived from aromatic ketones. The mode of action of one of the most active compound, the 3,4-dihydronaphtalen-1(2H)one thiosemicarbazone (tetralone thiosemicarbazone), was studied further. This TSC lacked virucidal effects on JUNV virions. Results from time of addition experiments and viral protein expression assays suggest that tetralone thiosemicarbazone inhibited a late stage in the replicative cycle of JUNV.

Animals↗

PubMed2002

Novel "hybrid" iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells.

We previously demonstrated that 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) and other aroylhydrazone chelators possess potent antineoplastic activity because of their ability to bind iron (Fe). From these studies, we identified structural components of the hydrazones that provide antineoplastic activity, namely the salicylaldehyde and 2-hydroxy-1-naphthylaldehyde moieties. A related group of chelators known as the thiosemicarbazones also show pronounced antitumor activity because of their ability to inhibit ribonucleotide reductase. Considering this, we designed a new series of "hybrid ligands" by condensation of the aldehydes described above with a range of thiosemicarbazides. The parent compound of these ligands is 2-hydroxy-1-naphthylaldehyde thiosemicarbazone (NT). Of 8 NT analogues, 3 chelators, namely NT, N4mT (2-hydroxy-1-naphthylaldehyde-4-methyl-3-thiosemicarbazone), and N44mT (2-hydroxy-1-naphthylaldehyde-4,4-dimethyl-3-thiosemicarbazone), showed high antiproliferative activity against SK-N-MC neuroepithelioma cells (50% inhibitory concentration [IC(50)] = 0.5-1.5 microM). Indeed, their activity was significantly (P <.0001) greater than that of desferrioxamine (DFO) (IC(50) = 22 microM). We demonstrate that 311, a 311 analogue (311m), and several NT-series chelators have significantly (P <.001) greater antiproliferative activity against tumor cells than against a range of normal cell types. For example, the IC(50) values of NT and N4mT in SK-N-MC neuroepithelioma cells were 0.5 microM, whereas for fibroblasts the IC(50) values were greater than 25 microM. Further, the effect of one of the most potent chelators (311m) on preventing the growth of bone marrow stem cell cultures was far less than that of doxorubicin and similar to that of cisplatin. These studies support the further development of these chelators as antiproliferative agents.

Antineoplastic Agents↗

PubMed2003

Oxidative cyclization of D-fructose thiosemicarbazones to 2-amino-5-(D-arabino-1,2,3,4-tetrahydroxybut-1-yl)-1,3,4-thiadiazoles through carbon-carbon bond cleavage of the sugar chain.

Condensation of D-fructose (1) with thiosemicarbazide or 4-phenylthiosemicarbazide gave the corresponding D-fructose thiosemicarbazones (3a and 3b). The latter compounds underwent oxidative cyclization with 10% ethanolic ferric chloride to give mixtures of 2-amino-5-(D-arabino-1,2,3,4-tetrahydroxybut-1-yl)-1,3,4-thiadiazole (6a) and 2-amino-5-hydroxymethyl-1,3,4-thiadiazole (5a) from 3a and the corresponding 2-phenylamino compounds 6b and 5b from 3b. These products were formed as a result of cyclization of the thiosemicarbazone entity accompanied by C-1-C-2 or C-2-C-3 bond cleavage of the sugar chain. Structures of the 1,3,4-thiadiazole acyclo C-nucleosides 6a and 5b were confirmed by comparison with the unequivocally prepared compounds obtained by the dehydrogenative cyclization of D-arabinose thiosemicarbazones 11a and 11b with ethanolic ferric chloride. Structures of the 5-hydroxymethyl-1,3,4-thiadiazoles 5a and 5b were also confirmed by comparison with 5a and 5b unequivocally prepared by periodate cleavage of the alditolyl chain of 6a and 6b followed by reduction of the resulting aldehydes 8a and 8b with sodium borohydride. Compounds 6a and 6b were further characterized as their acetates 7a and 7b and were found to exist in the extended planar zizag conformation 13. Condensative cyclization of the D-arabinose thiosemicarbazones 11a and 11b by boiling with acetic anhydride afforded the 1,3,4-thiadiazoline acyclo C-nucleoside acetates 9a and 9b which exist in the sickle (bent) conformation 14. De-N- and de-O-acetylation with concomitant aromatization of 9a and 9b with 10% ethanolic FeCl3 gave the 1,3,4-thiadiazole acyclo C-nucleosides 6a and 6b. The assigned structures were corroborated by 2D 1H-1H HOMCOR and 2D 1H-13C HETCOR NMR spectroscopy.

Acetylation↗

PubMed1990

[Synthesis and bacteriostatic activity of thiosemicarbazone and their transition metal complexes].

In this paper, 8 thiosemicarbazones and 12 transition metal complexes thereof have been synthesized and tested for bacteriostatic activity against five kinds of bacteria. The results show that hetero atom or substitution group in the o-position of the aryl ring to the carbonyl group in the aldehyde or ketone is essential to the bacteriostatic activity of the thiosemicarbazones, and different mechanisms of inhibition are followed by thiosemicarbazones and their complexes. The complexes displayed activity superior to the thiosemicarbazones.

Bacteria↗

PubMed1978

Steroidal derivatives. Part 1: some novel steroidal thiosemicarbazones. Their synthesis, anticancer and endocrinological activities.

The synthesis of several novel thiosemicarbazone derivatives of steroids, including estrogens and androgens, is described. Evaluation of the products in P 388 Lymphocytic Leukemia indicated no anticancer activity. The endocrinological screening showed that estrogenicity is slightly reduced but not abolished in the thiosemicarbazones derived from estrone-3-methyl ether (compounds 1, 2 and 4). The androgenic activity of the thiosemicarbazones derived from testosterone (compounds 7--9) was more pronounced than that of testosterone. Among the same thiosemicarbazone derivatives 7--9, only o-tolyl derivative 8 exhibited anabolic activity.

Animals↗

PubMed2000

Unusual coordination mode of thiosemicarbazone ligands. A search for the origin.

Twelve mixed-ligand thiosemicarbazone complexes of ruthenium and osmium, ten of general formula [M(bpy)2(bztsc-R)]ClO4, (M = Ru, Os; bpy = 2,2'-bipyridine, Hbztsc-R = benzaldehyde thiosemicacbazone) and two of type [M(bpy)2(actsc)]ClO4 (Hactsc = acetonethiosemicarbazone), have been synthesized and characterized. All the complexes are diamagnetic (low-spin d6, S = 0) and in acetonitrile solution show several intense metal-to-ligand charge-transfer (MLCT) transitions in the visible region. Structures of Hbztsc-OMe, [Ru(bpy)2(bztsc-NO2)]ClO4 and [Ru(bpy)2(actsc)]ClO4 have been determined by X-ray crystallography. Benzaldehyde thiosemicarbazone exists in the thione form with the phenyl group trans to the hydrazinic nitrogen. The benzaldehyde thiosemicarbazone ligand coordinates to the metals through the hydrazinic nitrogen and sulfur with a bite angle of approximately 67 degrees, forming a four-membered chelate ring. However, the actsc ligand coordinates through the imine nitrogen and sulfur, forming a five-membered chelate ring with a bite angle of approximately 81 degrees. The difference in coordination modes of two types of thiosemicarbazone ligands, viz., bztsc-R and actsc, appears to result from the difference in steric bulk of the aryl and methyl group trans to the hydrazinic nitrogen. In acetronitrile solution they all show a reversible metal(II)-metal(III) oxidation in the range 0.18-0.58 V vs SCE followed by an irreversible oxidation in the range 1.11-1.60 V vs SCE. Two successive one-electron reductions of the coordinated bipyridine are also observed in the range -1.53 to -1.96 V vs SCE.

Journal Article↗

PubMed1975

Arenavirus inactivation on contact with N-substituted isatin beta-thiosemicarbazones and certain cations.

N-methyl and N-ethyl isatin beta-thiosemicarbazones inactivate cell-free Parana and Pichinde viruses as well as three strains of lymphocytic choriomeningitis virus. This antiviral activity is abolished in the presence of the chelating agent EDTA. The rate of virus inactivation by N-methyl isatin beta-thiosemicarbazone is greatly enhanced and controlled by the addition of cupric sulphate. Divalent cations of other first transition series metals are less effective. A difference exists in the copper requirement for fast inactivation of the prototype arenavirus (lymphocytic choriomeningitis) and the Tacaribe Complex of viruses (Parana and Pichinde). In the presence of 20 muM-N-methyl isatin beta-thiosemicarbazone, LCM and Pichinde viruses can be inactivated at about the same rate if 20 muM-CuSO4 is added to the former and 160 muM-CuSO4 is added to the latter. Using 20 muM-N-methyl isatin beta-semicarbazone and CuSO4 the inactivation of LCM is reduced, but not eliminated, in the presence of an equal amount of infectious Pichinde virus. Crude and highly purified Pichinde virus are inactivated at the same rate when exposed to identical concentrations of N-methyl isatin beta-thiosemicarbazone and cupric sulphate. There is little detectable change in the inactivation rates when Pichinde or LCM viruses are grown in a variety of different cell lines.

Cell Line↗

PubMed1979

Studies on some new thiosemicarbazones as potential antitubercular agents.

Twenty-one 4-aryl-3-thiosemicarbazides and their new vanillin-4-aryl-3-thiosemicarbazones have been prepared in good yield. Antitubercular activity of five of the vanillin-4-aryl-3-thiosemicarbazones was evaluated against mycobacterium tuberculosis strain H37 Ra in Löwenstein-Jensen medium. In addition to IR, biological activity and TLC studies for thiosemicarbazones were carried out.

Antitubercular Agents↗

PubMed1982

Biodistribution of 59Fe-thiosemicarbazones.

The 59Fe-iron(II) chelates of 2-formylpyridine thiosemicarbazone (I), 5-dimethylamino-2-formylpyridine thiosemicarbazone (II), and 5-hydroxy-2-formylpyridine thiosemicarbazone (III) were prepared and their biodistribution determined in normal rats. Early accumulation of these complexes occurred in the liver, muscle and pelt with lesser amounts in the blood, kidneys and other organs. The tissue levels decreased with a 1 to 2-h half-life with the exception of the liver and intestines. The liver level tended to remain constant over the 2-h period. Accumulation in the gut resulting from hepatobiliary excretion increased over the first 60 min and then leveled off. In rats bearing a subcutaneous glioblastoma the uptake of compound I increased during the first 24 h after administration, and tumor to normal tissue ratios of 2 to 3.3 were obtained.

Animals↗

PubMed1988

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones.

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and Mössbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.

Animals↗

PubMed1986

Thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model.

A series of 111 thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds were evaluated as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model. All derivatives tested were potent inhibitors of virus replication with mean 50% inhibitory concentrations of 1.1 micrograms/ml for both type 1 and 2 herpes simplex virus. Inhibitory concentrations for cellular protein and DNA synthesis were considerably higher for many compounds resulting in in vitro therapeutic indices ranging from greater than 100 (highly selective) to less than 1 (negatively selective). All compounds were tested for dermal toxicity following topical administration of saturated solutions in 1,3-butanediol to the shaved, depilated skin of guinea pigs. Approximately 50% of the compounds produced slight to no dermal toxicity whereas the remaining compounds produced moderate to severe dermal toxicity. 28 compounds were evaluated in the cutaneous herpes guinea pig model against herpes simplex virus type 1. A number of N4-monosubstituted 2-acetylpyridine thiosemicarbazones produced highly significant reductions in days to healing and lesion score without producing untoward dermal toxicity. Structure-activity relationships revealed that a reduction of the azomethine bond in the molecule (i.e., conversion of a thiosemicarbazone to a thiosemicarbazide) greatly diminished dermal toxicity apparently without producing a proportional decrease in antiviral activity.

Animals↗