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Sample records for 3-deoxy-d-erythro-hexos-2-ulose bis thiosemicarbazone

  1. Kinetics of 3-deoxy-D-erythro-hexos-2-ulose in unifloral honeys.

    PubMed

    Arena, Elena; Ballistreri, Gabriele; Fallico, Biagio

    2011-09-01

    In this study, for the first time, the amount of 3-deoxy-D-erythro-hexos-2-ulose (3-DG) in fresh citrus and chestnut honeys was determined. 3-DG was measured as the corresponding quinoxalines after derivatization with orthophenylenediamine using reverse-phase high-performance liquid chromatography (RP-HPLC). Notwithstanding the freshness of the samples, high levels of 3-DG were detected in both honeys. The comparison of 3-DG and 5-hydroxymethylfurfural (HMF) concentrations, which was also quantified by RP-HPLC, showed that citrus honeys had the lowest amount of 3-DG (107 mg/kg) and the highest of HMF (16.7 mg/kg), while chestnut honeys had the opposite (398 and 1.2 mg/kg, respectively). During thermal treatment, different 3-DG and HMF trends were highlighted between the citrus and chestnut honeys; at the end, 3-DG formation was more favored with respect to HMF formation. Moreover, in citrus honeys, a good correlation between 3-DG and HMF levels was observed, which was not found in chestnut honeys, suggesting a role of the high pH values of these honeys on the degradation routes. The kinetic analysis showed the highest k value for 3-DG and HMF formation in chestnut and citrus honeys, respectively. The lowest Ea values related to 3-DG formation and the highest to HMF formation, indicating that the key intermediate 3-DG is easily formed at low temperatures, whilst the formation of HMF requires higher temperatures. For this reason, 3-DG seems to be an aging index rather than a thermal index and its use, at least for honeys at high pH values, together with HMF, could improve their quality assessment. PMID:22417541

  2. Cu, Pt, and Pd complexes of the 3-deoxy-1,2-bis(thiosemicarbazone) derived from D-glucose.

    PubMed

    Horton, D; Varela, O

    2000-09-22

    3-Deoxy-D-erythro-hexos-2-ulose bis(thiosemicarbazone) (1) acts as a tetradentate ligand of the N2S2 type which forms stable coordination complexes with metal(II) cations. The Cu(II), Pt(II), and Pd(II) chelates (2, 4, and 6, respectively) of 1 were synthesized and characterized by elemental analysis and NMR spectroscopy. The NMR spectra of the Pt complex (4) showed the coupling of H-1 and C-1, C-2 of the bis(thiosemicarbazone) with 195Pt (33.7% naturally occurring), which supports the structure proposed for the chelate. The complexes 2, 4, and 6 were acetylated to give the corresponding tri-O-acetyl derivatives 3, 5, and 7. Elimination of Cu(II) from 3 with hydrogen sulfide afforded 8, the tri-O-acetyl derivative of 1. Preliminary studies have shown antiviral activity of chelates 2, 4, and 6 against poliovirus type 1. PMID:11072850

  3. Species Dependence of [64Cu]Cu-Bis(thiosemicarbazone) Radiopharmaceutical Binding to Serum Albumins

    PubMed Central

    Basken, Nathan E.; Mathias, Carla J.; Lipka, Alexander E.; Green, Mark A.

    2008-01-01

    Introduction Interactions of three copper(II) bis(thiosemicarbazone) PET radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods 64Cu-labeled diacetyl bis(N4-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II) (Cu-PTSM), and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon, and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat, and mouse serum. Results The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/mL, “% Free” (non-albumin-bound) levels of radiopharmaceutical were 4.0 ± 0.1%; 5.3 ± 0.2%; and 38.6 ± 0.8% for Cu-PTSM; Cu-ATSM; and Cu-ETS, respectively. Conclusions Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans. PMID:18355683

  4. Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization.

    PubMed

    Stefani, Christian; Al-Eisawi, Zaynab; Jansson, Patric J; Kalinowski, Danuta S; Richardson, Des R

    2015-11-01

    Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) Cu(II/I) redox potentials; (2) ability to induce cellular (64)Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-l-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones). PMID:26335599

  5. Diphenyllead(IV) chloride complexes with benzilthiosemicarbazones. The first bis(thiosemicarbazone) derivatives.

    PubMed

    Calatayud, David G; López-Torres, Elena; Mendiola, M Antonia

    2007-11-26

    Reactions of diphenyllead(IV) chloride with benzil bis(thiosemicarbazone) (L1H6) and benzil bis(4-methyl-3-thiosemicarbazone) (L1Me2H4) afforded the first complexes containing the diphenyllead(IV) moiety with bis(thiosemicarbazone) ligands. The new complexes show diverse structural characteristics depending on the ligand and the working conditions. Complexes [PbPh2Cl(L1H5)].3H2O (1) and [PbPh2Cl(L1Me2H3)] (3) are mononuclear species in which the ligands are partially deprotonated and the lead atom has a C2N2S2Cl environment in a distorted pentagonal bipyramid coordination geometry. Complex [PbPh(L1Me2H2)](2).2H2O (4) was also obtained, which contains two lead atoms in a binuclear structure with a C2N2S3 coordination sphere for each lead atom, since both dideprotonated ligands act as N2S2 chelate and as sulfur bridge. Reaction from L1H6, in the same conditions in which complex 4 was prepared, gave a mixture of products: the lead (II) complex [Pb(L1H4)]2 (2) and [PbPh3Cl]n. Reactions with the cyclic molecules 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]-triazine-3-thione (L2H2OCH3) and 5-methoxy-4-methyl-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]-triazine-3-thione (L2MeHOCH3) were also explored. In all the complexes, the ligands are deprotonated. The complexes [PbPh2(L2)2] (5) and [PbPh2(L2MeOCH3)2] (7) present the same characteristics. The X-ray structure of 5 shows a distorted octahedral geometry around the lead atom, with the ligand molecules acting as NS chelates, but the nitrogen bonded to the metal is different; one of the triazines shows a novel behavior, since the nitrogen atom of the new imine group formed is the one that is bonded to the lead center, being a good example of linkage isomerism. The complex [PbPh2Cl(L2)] (6), which was also isolated, could not be crystallized. All the complexes were characterized by elemental analysis, mass spectrometry, IR and 1H, 13C, and 207Pb NMR spectroscopy and some of them by X-ray diffraction studies. PMID:17939655

  6. Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals.

    PubMed

    Paterson, Brett M; Donnelly, Paul S

    2011-05-01

    The molecules known as bis(thiosemicarbazones) derived from 1,2-diones can act as tetradentate ligands for Cu(II), forming stable, neutral complexes. As a family, these complexes possess fascinating biological activity. This critical review presents an historical perspective of their progression from potential chemotherapeutics through to more recent applications in nuclear medicine. Methods of synthesis are presented followed by studies focusing on their potential application as anti-cancer agents and more recent investigations into their potential as therapeutics for Alzheimer's disease. The Cu(II) complexes are of sufficient stability to be used to coordinate copper radioisotopes for application in diagnostic and therapeutic radiopharmaceuticals. Detailed understanding of the coordination chemistry has allowed careful manipulation of the metal based properties to engineer specific biological activities. Perhaps the most promising complex radiolabelled with copper radioisotopes to date is Cu(II)(atsm), which has progressed to clinical trials in humans (162 references). PMID:21409228

  7. Comparative analysis of the cytotoxicity of substituted (phenylglyoxal bis(4-methyl-3-thiosemicarbazone)) copper (II) chelates.

    PubMed

    Coats, E A; Milstein, S R; Holbein, G; McDonald, J; Reed, R; Petering, H G

    1976-01-01

    Seven para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)]copper (II) chelates (12-18) have been designed, synthesized, and tested for their ability to inhibit the respiration of rat liver slices as a normal cell model and Ehrlich ascites cells as a tumor cell model. Relationships between chemical structure and respiratory inhibition are described on a quantitative basis using substituent contants (pi, Es, and sigmap) by computerized multiparameter regression analyses. The correlations indicate that changes in Es have the largest effect on liver slice toxicity of chelates while pi and sigmap account for most of the variation in toxicity to ascites cells. A comparative analysis strongly suggests that electron-donating substituents with greater water solubility should increase cytotoxicity to ascites cells at the expense of cytotoxicity to the rat liver cells. The predictions of the equations were checked by synthesizing and testing an additional derivative. The results strengthen the initial predictions. PMID:1246035

  8. Preparation and Biodistribution Studies of a Radiogallium-Acetylacetonate Bis (Thiosemicarbazone) Complex in Tumor-Bearing Rodents

    PubMed Central

    Jalilian, Amir Reza; Yousefnia, Hassan; Shafaii, Kamaleddin; Novinrouz, Aytak; Rajamand, Amir Abbas

    2012-01-01

    Various radiometal complexes have been developed for tumor imaging, especially Ga-68 tracer. In the present study, the development of a radiogallium bis-thiosemicarbazone complex has been reported. [67Ga] acetylacetonate bis(thiosemicarbazone) complex ([67Ga] AATS) was prepared starting [67Ga]Gallium acetate and freshly prepared acetylacetonate bis (thiosemicarbazone) (AATS) in 30 min at 90°C. The partition co-efficient and the stability of the tracer were determined in final solution (25°C) and the presence of human serum (37°C) up to 24 h. The biodistribution of the labeled compound in wild-type and fibrosarcoma-bearing rodents were determined up to 72 h. The radiolabled Ga complex was prepared in high radiochemical purity (> 97%, HPLC) followed by initial biodistribution data with the significant tumor accumulation of the tracer in 2 h which is far higher than free Ga-67 cation while the compound wash-out is significantly faster. Above-mentioned pharmacokinetic properties suggest an interesting radiogallium complex while prepared by the PET Ga radioisotope, 68Ga, in accordance with the physical half life, for use in fibrosarcoma tumors, and possibly other malignancies. PMID:24250475

  9. Synthesis and spectral investigations of Mn(II) complexes of pentadentate bis(thiosemicarbazones)

    NASA Astrophysics Data System (ADS)

    Krishnan, Suja; Laly, K.; Prathapachandra Kurup, M. R.

    2010-02-01

    Five Mn(II) complexes of bis(thiosemicarbazones) which are represented as [Mn(H 2Ac4Ph)Cl 2] ( 1), [Mn(Ac4Ph)H 2O] ( 2), [Mn(H 2Ac4Cy)Cl 2]·H 2O ( 3), [Mn(H 2Ac4Et)Cl 2]·3H 2O ( 4) and [Mn(H 2Ac4Et)(OAc) 2]·3H 2O ( 5) have been synthesized and characterized by elemental analyses, electronic, infrared and EPR spectral techniques. In all the complexes except [Mn(Ac4Ph)H 2O], the ligands act as pentadentate neutral molecules and coordinate to Mn(II) ion through two thione sulfur atoms, two azomethine nitrogens and the pyridine nitrogen, suggesting a heptacoordination. While in compound [Mn(Ac4Ph)H 2O], the dianionic ligand is coordinated to the metal suggesting six coordination in this case. Magnetic studies indicate the high spin state of Mn(II). Conductivity measurements reveal their non-electrolyte nature. EPR studies indicate five g values for [Mn(Ac4Ph)H 2O] showing zero field splitting.

  10. Toxic effects of bis(thiosemicarbazone) compounds and its palladium(II) complexes on herpes simplex virus growth.

    PubMed

    Genova, Petia; Varadinova, Tatiana; Matesanz, Ana I; Marinova, Desislava; Souza, Pilar

    2004-06-01

    Here, we present data on the activity of benzyl bis(thiosemicarbazone); 3,5-diacyl-1,2,4-triazole bis(4-methylthiosemicarbazone) and their Pd(II) complexes against the replication of wild type and of acyclovir (ACV)-resistant, herpes simplex virus type 1 (HSV 1) and type 2 (HSV 2) strains. The data were compared to those under the action of acyclovir. The testing of cytotoxic activity suggests that these compounds may be endowed with important antiviral properties. It is interesting to note that the Pd(II)-benzyl bis(thiosemicarbazone) complex, 2, exhibits a significant activity against acyclovir-resistant viruses R-100 (HSV 1) and PU (HSV 2) with an in vitro selectivity index (SI) of 8.0 vs. 0.01 for acyclovir. This complex also negatively influenced the expression of key structural HSV 1 proteins (VP23, gH and gG/gD), thus suppressing simultaneously virus entry, transactivation of virus genome, capsid assembly, and cell-to-cell spread of infectious HSV progeny. PMID:15163546

  11. Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging

    NASA Astrophysics Data System (ADS)

    Singh, Sweta; Tiwari, Anjani K.; Varshney, Raunak; Mathur, R.; Shukla, Gauri; Bag, N.; Singh, B.; Mishra, Anil K.

    2016-01-01

    2,2‧,2″-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11-tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N-methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2-ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized and evaluated for imaging application. The pharmacokinetics of these ligands were determined by tracer methods. In vitro human serum stability of 99mTc Met-ac-TE3A/99mTc Bis(thiosemicarbazone)-Biotin after 24 h was found to be 96.5% and 97.0% respectively. Blood kinetics of both ligands in normal rabbits showed biphasic clearance pattern. Ex vivo biodistribution study revealed significant initial tumor uptake and high tumor/muscles ratio which is a pre-requisite condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging.

  12. Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging.

    PubMed

    Singh, Sweta; Tiwari, Anjani K; Varshney, Raunak; Mathur, R; Shukla, Gauri; Bag, N; Singh, B; Mishra, Anil K

    2016-01-15

    2,2',2″-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11-tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N-methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2-ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized and evaluated for imaging application. The pharmacokinetics of these ligands were determined by tracer methods. In vitro human serum stability of (99m)Tc Met-ac-TE3A/(99m)Tc Bis(thiosemicarbazone)-Biotin after 24h was found to be 96.5% and 97.0% respectively. Blood kinetics of both ligands in normal rabbits showed biphasic clearance pattern. Ex vivo biodistribution study revealed significant initial tumor uptake and high tumor/muscles ratio which is a pre-requisite condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging. PMID:26436844

  13. Binuclear ruthenium(III) bis(thiosemicarbazone) complexes: Synthesis, spectral, electrochemical studies and catalytic oxidation of alcohol

    NASA Astrophysics Data System (ADS)

    Mohamed Subarkhan, M.; Ramesh, R.

    2015-03-01

    A new series of binuclear ruthenium(III) thiosemicarbazone complexes of general formula [(EPh3)2(X)2Ru-L-Ru(X)2(EPh3)2] (where E = P or As; X = Cl or Br; L = NS chelating bis(thiosemicarbazone ligands) has been synthesized and characterized by analytical and spectral (FT-IR, UV-Vis and EPR). IR spectra show that the thiosemicarbazones behave as monoanionic bidentate ligands coordinating through the azomethine nitrogen and thiolate sulphur. The electronic spectra of the complexes indicate that the presence of d-d and intense LMCT transitions in the visible region. The complexes are paramagnetic (low spin d5) in nature and all the complexes show rhombic distortion around the ruthenium ion with three different 'g' values (gx ≠ gy ≠ gz) at 77 K. All the complexes are redox active and exhibit an irreversible metal centered redox processes (RuIII-RuIII/RuIV-RuIV; RuIII-RuIII/RuII-RuII) within the potential range of 0.38-0.86 V and -0.39 to -0.66 V respectively, versus Ag/AgCl. Further, the catalytic efficiency of one of the complexes [Ru2Cl2(AsPh3)4(L1)] (4) has been investigated in the case of oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of N-methylmorpholine-N-oxide(NMO) as co-oxidant. The formation of high valent RuVdbnd O species is proposed as catalytic intermediate for the catalytic cycle.

  14. Binuclear ruthenium(III) bis(thiosemicarbazone) complexes: synthesis, spectral, electrochemical studies and catalytic oxidation of alcohol.

    PubMed

    Mohamed Subarkhan, M; Ramesh, R

    2015-03-01

    A new series of binuclear ruthenium(III) thiosemicarbazone complexes of general formula [(EPh3)2(X)2Ru-L-Ru(X)2(EPh3)2] (where E=P or As; X=Cl or Br; L=NS chelating bis(thiosemicarbazone ligands) has been synthesized and characterized by analytical and spectral (FT-IR, UV-Vis and EPR). IR spectra show that the thiosemicarbazones behave as monoanionic bidentate ligands coordinating through the azomethine nitrogen and thiolate sulphur. The electronic spectra of the complexes indicate that the presence of d-d and intense LMCT transitions in the visible region. The complexes are paramagnetic (low spin d(5)) in nature and all the complexes show rhombic distortion around the ruthenium ion with three different 'g' values (gx≠gy≠gz) at 77K. All the complexes are redox active and exhibit an irreversible metal centered redox processes (Ru(III)-Ru(III)/Ru(IV)-Ru(IV); Ru(III)-Ru(III)/Ru(II)-Ru(II)) within the potential range of 0.38-0.86V and -0.39 to -0.66 V respectively, versus Ag/AgCl. Further, the catalytic efficiency of one of the complexes [Ru2Cl2(AsPh3)4(L1)] (4) has been investigated in the case of oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of N-methylmorpholine-N-oxide(NMO) as co-oxidant. The formation of high valent Ru(V)O species is proposed as catalytic intermediate for the catalytic cycle. PMID:25498823

  15. Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia.

    PubMed

    Alam, Israt S; Arrowsmith, Rory L; Cortezon-Tamarit, Fernando; Twyman, Frazer; Kociok-Köhn, Gabriele; Botchway, Stanley W; Dilworth, Jonathan R; Carroll, Laurence; Aboagye, Eric O; Pascu, Sofia I

    2016-01-01

    We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under 'cold' and 'hot' biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. (68)Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration. PMID:26583314

  16. comparative analysis of cellular respiratory inhibition by substituted phenylglyoxal-bis-(4-methyl-3-thiosemicarbazone) zinc chelates.

    PubMed

    Coats, E A; Milstein, S R; Pleiss, M A; Roesener, J A; Schmidt, J; McDonald, J; Reed, R

    1983-03-01

    Fourteen para-substituted phenylglyoxal-bis-(4-methyl-3-thiosemicarbazone) zinc chelates have been synthesized as inhibitors of cellular respiration and therefore as potential antineoplastic agents. Each chelate has been evaluated as an inhibitor of Ehrlich ascites tumor cell and of rat liver slice respiration. The molar I50 values for respiratory inhibition have been subjected to computerized correlation to delineate quantitative relationships between biological activity and chemical structure. Activity against the tumor cell model is characterized by a positive lipophilic and a detrimental steric influence while activity against rat liver slice displays only a weak positive lipophilic effect. Quantitative comparative analysis suggests that selective action against the tumor cell system can be improved by substituents which are electron withdrawing and lipophilic in nature. PMID:6852227

  17. Synthetic, structural and kinetic studies on the binding of cyclohexane-1,2-bis(4-methyl-3-thiosemicarbazone) to divalent metal ions (Co, Ni, Cu, Zn or Cd).

    PubMed

    Al-Karawi, Ahmed Jasim M; Clegg, William; Harrington, Ross W; Henderson, Richard A

    2009-01-21

    The reactions of cyclohexane-1,2-bis(4-methyl-3-thiosemicarbazone) (CHMTSC) with MCl2 (M = Co, Ni, Cu or Zn) and Cd(NO3)2 have been shown to produce complexes in which the thiosemicarbazone has been doubly deprotonated [[M(CHMTSC - 2H+)] (M = Co, Ni or Ni)], analogous to those reported earlier with other Schiff base thiosemicarbazones. However, with ZnCl2 and Cd(NO3)2, the complexes isolated are [ZnCl(CHMTSC)]Cl and [Cd(NO3)(CHMTSC)]NO3, containing the protonated forms of the ligand, which have been characterised by X-ray crystallography, as has free CHMTSC. The kinetics of the reactions between CHMTSC and all the various metal salts have been determined by stopped-flow spectrophotometry. In all cases, the reactions are complete on the seconds timescale. The reactions exhibit a first-order dependence on the concentration of metal salt and a first-order dependence on the concentration of CHMTSC. The thermodynamic and kinetic factors influencing the protonation state of the coordinated thiosemicarbazone are discussed. PMID:19122915

  18. A novel zinc bis(thiosemicarbazone) complex for live cell imaging.

    PubMed

    Dayal, Disha; Palanimuthu, Duraippandi; Shinde, Sridevi Vijay; Somasundaram, Kumaravel; Samuelson, Ashoka G

    2011-04-01

    Fluorescent zinc complexes have recently attracted a lot of interest owing to their vast applications in cellular imaging. We report the synthesis as well as physical, chemical and biological studies of a novel zinc glyoxalbis(4-methyl-4-phenyl-3-thiosemicarbazone), [Zn(GTSC)]₃, complex. As compared with the well-studied zinc biacetylbis(4-methyl-3-thiosemicarbazone), Zn(ATSM), complex, which was used as a reference, [Zn(GTSC)]₃ had 2.5-fold higher fluorescence. When cellular fluorescence was measured using flow cytometry, we observed that [Zn(GTSC)]₃ had 3.4-fold to 12-fold higher fluorescence than Zn(ATSM) in various cell lines (n = 9) of different tissue origin. Confocal fluorescence microscopy results showed that [Zn(GTSC)]₃ appeared to have a nuclear localization within 30 min of addition to MCF7 cells. Moreover, [Zn(GTSC)]₃ showed minimal cytotoxicity compared with Zn(ATSM), suggesting that [Zn(GTSC)]₃ may be less deleterious to cells when used as an imaging agent. Our data suggest that the novel [Zn(GTSC)]₃ complex can potentially serve as a biocompatible fluorescent imaging agent for live cells. PMID:21384247

  19. A dual radiolabelling approach for tracking metal complexes: investigating the speciation of copper bis(thiosemicarbazonates) in vitro and in vivo.

    PubMed

    Hueting, Rebekka; Kersemans, Veerle; Tredwell, Matthew; Cornelissen, Bart; Christlieb, Martin; Gee, Antony D; Passchier, Jan; Smart, Sean C; Gouverneur, Véronique; Muschel, Ruth J; Dilworth, Jonathan R

    2015-05-01

    Copper(II)bis(thiosemicarbazonato) complexes such as [(64)Cu]Cu-ATSM continue to be investigated for positron emission tomography (PET) imaging of tumour hypoxia. However, the currently proposed mechanisms for the mode of action of these complexes are unable to account fully for their observed biological behaviour. In order to examine the roles of the copper metal and the ligand, we designed a pair of (123)I/(64)Cu-copper bis(thiosemicarbazonates), radiolabelled at either the metal or at the ligand. In vitro cellular retention studies of the orthogonal pair demonstrate for the first time that retention under hypoxia involves dissociation of the copper bis(thiosemicarbazone) complex, consistent with the previously suggested mechanism of reductive trapping of copper. In contrast, in vivo biodistribution and dynamic PET/SPECT imaging of the orthogonally labelled complexes underline our previous findings for [(64)Cu]Cu-ATSM and [(64)Cu]Cu-acetate, providing further support for the important contribution of copper metabolism in the in vivo hypoxia selectivity of Cu-ATSM. This dual radiolabelling approach may find applications for determining the speciation of other metal complexes in vitro and in vivo. PMID:25768310

  20. Comparative analysis of the cytotoxicity of substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates. 2. Parabolic correlations and their implications for selective toxicity.

    PubMed

    Coats, E A; Milstein, S R; Pleiss, M A; Roesener, J A

    1978-08-01

    The synthesis of an extended series of para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates is reported. Subsequent biological evaluation and regression analysis have been performed, correlating pI50 with extrathermodynamic substituent parameters. Parabolic correlations with pi have resulted which predict optimum lipophilic character of the para substituent with respect to Ehrlich ascites cytotoxicity (pi0 = -2.13) and with respect to ascites vs. liver slice cytotoxicity (pi0 = -1.31). Results indicated clearly that the chelate most toxic to the tumor cell model may not be the most selective. PMID:691005

  1. Cu(II) Bis(thiosemicarbazone) Radiopharmaceutical Binding to Serum Albumin: Further Definition of Species-Dependence and Associated Substituent Effects

    PubMed Central

    Basken, Nathan E.; Green, Mark A.

    2009-01-01

    Introduction The Cu-PTSM (pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N4-methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) radiopharmaceutical appears to only exhibit non-specific binding to human and animal serum albumins. Methods To further probe the structural basis for the species-dependence of this albumin binding interaction, protein binding of these three radiopharmaceuticals was examined in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat, elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species-dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate. PMID:19520290

  2. Partial conversion of thioamide into nitrile in a copper(II) complex of 2,6-diacetylpyridine bis(thiosemicarbazone), a drug prototype for Alzheimer's disease.

    PubMed

    Vieira, Rafael P; Thompson, John R; Beraldo, Heloisa; Storr, Tim

    2015-06-01

    This work reports the crystal structure of [(Z)-2-((E)-1-{6-[1-({[amino(sulfanidyl-κS)methylidene]amino}imino-κN)ethyl]pyridin-2-yl-κN}ethylidene)-1-cyanohydrazinido-κN(1)]copper(II), [Cu(C11H11N7S)], the first description of a copper(II) complex of 2,6-diacetylpyridine bis(thiosemicarbazone) showing partial conversion of a thioamide group to a nitrile group. The asymmetric ligand coordinates to the metal centre in an N,N',N'',S-tetradentate manner via the pyridine N atom, an imine N atom, the hydrazinide N atom and the sulfanidyl S atom, displaying a square-planar geometry. Ligand coordination results in two five-membered chelate rings and one six-membered chelate ring, and in crystal packing based on N-H···N hydrogen bonds of the cyanohydrazinide and hydrazinecarbothioamidate arms of the ligand. The correlation between the partial conversion upon metal complexation, H2S release and possible effects on the activity of bis(thiosemicarbazone)s as drug prototypes for Alzheimer's disease is also discussed. PMID:26044321

  3. Simultaneous spectrophotometric determination of copper, cobalt, nickel and iron in foodstuffs and vegetables with a new bis thiosemicarbazone ligand using chemometric approaches.

    PubMed

    Rohani Moghadam, Masoud; Poorakbarian Jahromi, Sayedeh Maria; Darehkordi, Ali

    2016-02-01

    A newly synthesized bis thiosemicarbazone ligand, (2Z,2'Z)-2,2'-((4S,5R)-4,5,6-trihydroxyhexane-1,2-diylidene)bis(N-phenylhydrazinecarbothioamide), was used to make a complex with Cu(2+), Ni(2+), Co(2+) and Fe(3+) for their simultaneous spectrophotometric determination using chemometric methods. By Job's method, the ratio of metal to ligand in Ni(2+) was found to be 1:2, whereas it was 1:4 for the others. The effect of pH on the sensitivity and selectivity of the formed complexes was studied according to the net analyte signal (NAS). Under optimum conditions, the calibration graphs were linear in the ranges of 0.10-3.83, 0.20-3.83, 0.23-5.23 and 0.32-8.12 mg L(-1) with the detection limits of 2, 3, 4 and 10 μg L(-1) for Cu(2+), Co(2+), Ni(2+) and Fe(3+) respectively. The OSC-PLS1 for Cu(2+) and Ni(2+), the PLS1 for Co(2+) and the PC-FFANN for Fe(3+) were selected as the best models. The selected models were successfully applied for the simultaneous determination of elements in some foodstuffs and vegetables. PMID:26304369

  4. Copper-64 radiolabelling of the C2A domain of synaptotagmin I using a functionalised bis(thiosemicarbazone): A pre- and post-labelling comparison.

    PubMed

    Hueting, Rebekka; Tavaré, Richard; Dilworth, Jonathan R; Mullen, Gregory E

    2013-11-01

    Dysregulation of apoptosis and necrosis is central to many diseases and non-invasive imaging of cell death is an important clinical objective to stage disease or to monitor treatment progress. The C2A domain of rat synaptotagmin I binds to phosphatidylserine (PS) exposed during cell death and modification to its lysine residues has been shown to disrupt PS binding. Site-specifically labelled (99m)Tc(CO)3-C2AcH and (68)Ga-C2Ac have previously been investigated for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging, respectively. We wished to design a (64)Cu-labelled counterpart due to the longer half-life of (64)Cu. Since the calcium binding sites in C2A may interfere with copper binding we sought a high affinity, fast labelling chelator. We synthesised a maleimide functionalised bis(thiosemicarbazone), H2ATSE/AMal, for the site-specific copper-64 radiolabelling of thiol-functionalised C2Ac. When radiolabelling was performed by incubation of the ligand-protein conjugate (post-labelling approach), analysis of the resultant (64)CuATSE/AMal-C2Ac revealed that the C2Ac was able to compete for radiocopper with the chelator. In contrast, the pre-labelled (64)CuATSE/AMal-C2Ac conjugate revealed good stability in serum and maintained target affinity in a red blood cell binding assay. The results suggest that due to the intrinsic copper binding properties of the protein, a pre-labelling approach is preferred for the C2Ac domain of synaptotagmin I when copper is the desired radioisotope. PMID:23954480

  5. Antiretroviral activity of thiosemicarbazone metal complexes.

    PubMed

    Pelosi, Giorgio; Bisceglie, Franco; Bignami, Fabio; Ronzi, Paola; Schiavone, Pasqualina; Re, Maria Carla; Casoli, Claudio; Pilotti, Elisabetta

    2010-12-23

    Thiosemicarbazones display a wide antimicrobial activity by targeting bacteria, fungi, and viruses. Here, we report our studies on the antiviral activity of two thiosemicarbazone metal complexes, [bis(citronellalthiosemicarbazonato)nickel(II)] and [aqua(pyridoxalthiosemicarbazonato)copper(II)] chloride monohydrate, against the retroviruses HIV-1 and HTLV-1/-2. Both compounds exhibit antiviral properties against HIV but not against HTLVs . In particular, the copper complex shows the most potent anti-HIV activity by acting at the post-entry steps of the viral cycle. PMID:21121632

  6. Iron and Cobalt Complexes of 2,6-Diacetylpyridine-bis(R-thiosemicarbazone) (R=H, phenyl) Showing Unprecedented Ligand Deviation from Planarity

    PubMed Central

    Panja, Anangamohan; Campana, Charles; Leavitt, Christopher; Van Stipdonk, Michael J.; Eichhorn, David M.

    2009-01-01

    The syntheses, characterization, and single-crystal X-ray crystal structures are reported for four complexes of iron and cobalt with the pentadentate ligands, 2,6-diacetylpyridinebis(thiosemicarbazone) (H2L1) and 2,6-diacetylpyridinebis-(phenylthiosemicarbazone) (H2L2), including a cobalt dimer displaying a deviation from planarity which is unprecedented for this class of ligands and allows the ligand to occupy five positions of a pseudo-octahedral coordination sphere. This dimer reacts with KCN to produce a mononuclear complex of relevance to the active site of cobalt nitrile hydratase. PMID:20161238

  7. Synthesis, structure and antifungal activity of thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) and nickel(II), copper(II) and cadmium(II) complexes: unsymmetrical coordination mode of nickel complex.

    PubMed

    Alomar, Kusaï; Landreau, Anne; Allain, Magali; Bouet, Gilles; Larcher, Gérald

    2013-09-01

    The reaction of nickel(II), copper(II) chlorides and cadmium(II) chloride and bromide with thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) (2,3BTSTCH2) leads to a series of new complexes: [Ni(2,3BTSTCH)]Cl, [Cu(2,3BTSTC)], [CdCl2(2,3BTSTCH2)] and [CdBr2(2,3BTSTCH2)]. The crystal structures of the ligand and of [Ni(2,3BTSTCH)]Cl complex have been determined. In this case, we remark an unusual non-symmetrical coordination mode for the two functional groups: one acting as a thione and the second as a deprotonated thiolate. All compounds have been tested for their antifungal activity against human pathogenic fungi: Candida albicans, Candida glabrata and Aspergillus fumigatus, the cadmium complexes exhibit the highest antifungal activity. Cytotoxicity was evaluated using two biological methods: human MRC5 cultured cells and brine shrimp Artemia salina bioassay. PMID:23792913

  8. Identification and quantification of six major α-dicarbonyl process contaminants in high-fructose corn syrup.

    PubMed

    Gensberger, Sabrina; Mittelmaier, Stefan; Glomb, Marcus A; Pischetsrieder, Monika

    2012-07-01

    High-fructose corn syrup (HFCS) is a widely used liquid sweetener produced from corn starch by hydrolysis and partial isomerization of glucose to fructose. During these processing steps, sugars can be considerably degraded, leading, for example, to the formation of reactive α-dicarbonyl compounds (α-DCs). The present study performed targeted screening to identify the major α-DCs in HFCS. For this purpose, α-DCs were selectively converted with o-phenylendiamine to the corresponding quinoxaline derivatives, which were analyzed by liquid chromatography with hyphenated diode array-tandem mass spectrometry (LC-DAD-MS/MS) detection. 3-Deoxy-D-erythro-hexos-2-ulose (3-deoxyglucosone), D-lyxo-hexos-2-ulose (glucosone), 3-deoxy-D-threo-hexos-2-ulose (3-deoxygalactosone), 1-deoxy-D-erythro-hexos-2,3-diulose (1-deoxyglucosone), 3,4-dideoxyglucosone-3-ene, methylglyoxal, and glyoxal were identified by enhanced mass spectra as well as MS/MS product ion spectra using the synthesized standards as reference. Addition of diethylene triamine pentaacetic acid and adjustment of the derivatization conditions ensured complete derivatization without de novo formation for all identified α-DCs in HFCS matrix except for glyoxal. Subsequently, a ultra-high performance LC-DAD-MS/MS method was established to quantify 3-deoxyglucosone, glucosone, 3-deoxygalactosone, 1-deoxyglucosone, 3,4-dideoxyglucosone-3-ene, and methylglyoxal in HFCS. Depending on the α-DC compound and concentration, the recovery ranged between 89.2% and 105.8% with a relative standard deviation between 1.9% and 6.5%. Subsequently, the α-DC profiles of 14 commercial HFCS samples were recorded. 3-Deoxyglucosone was identified as the major α-DC with concentrations up to 730 μg/mL HFCS. The total α-DC content ranged from 293 μg/mL to 1,130 μg/mL HFCS. Significantly different α-DC levels were not detected between different HFCS specifications, but between samples of various manufacturers indicating that the

  9. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L.

    PubMed

    Parker, Erica N; Song, Jiangli; Kishore Kumar, G D; Odutola, Samuel O; Chavarria, Gustavo E; Charlton-Sevcik, Amanda K; Strecker, Tracy E; Barnes, Ashleigh L; Sudhan, Dhivya R; Wittenborn, Thomas R; Siemann, Dietmar W; Horsman, Michael R; Chaplin, David J; Trawick, Mary Lynn; Pinney, Kevin G

    2015-11-01

    Upregulation of cathepsin L in a variety of tumors and its ability to promote cancer cell invasion and migration through degradation of the extracellular matrix suggest that cathepsin L is a promising biological target for the development of anti-metastatic agents. Based on encouraging results from studies on benzophenone thiosemicarbazone cathepsin inhibitors, a series of fourteen benzoylbenzophenone thiosemicarbazone analogues were designed, synthesized, and evaluated for their inhibitory activity against cathepsins L and B. Thiosemicarbazone inhibitors 3-benzoylbenzophenone thiosemicarbazone 1, 1,3-bis(4-fluorobenzoyl)benzene thiosemicarbazone 8, and 1,3-bis(2-fluorobenzoyl)-5-bromobenzene thiosemicarbazone 32 displayed the greatest potency against cathepsin L with low IC50 values of 9.9 nM, 14.4 nM, and 8.1 nM, respectively. The benzoylbenzophenone thiosemicarbazone analogues evaluated were selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10 μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5 μM. The most active cathepsin L inhibitors from this benzoylbenzophenone thiosemicarbazone series (1, 8, and 32) displayed low cytotoxicity toward normal primary cells [in this case human umbilical vein endothelial cells (HUVECs)]. In an initial in vivo study, 3-benzoylbenzophenone thiosemicarbazone (1) was well-tolerated in a CDF1 mouse model bearing an implanted C3H mammary carcinoma, and showed efficacy in tumor growth delay. Low cytotoxicity, inhibition of cell invasion, and in vivo tolerability are desirable characteristics for anti-metastatic agents functioning through an inhibition of cathepsin L. Active members of this structurally diverse group of benzoylbenzophenone thiosemicarbazone cathepsin L inhibitors show promise as potential anti-metastatic, pre

  10. Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia† †Electronic supplementary information (ESI) available. CCDC 1001632–1001634. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5dt02537k Click here for additional data file. Click here for additional data file.

    PubMed Central

    Alam, Israt S.; Arrowsmith, Rory L.; Cortezon-Tamarit, Fernando; Twyman, Frazer; Kociok-Köhn, Gabriele; Botchway, Stanley W.; Dilworth, Jonathan R.

    2016-01-01

    We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under ‘cold’ and ‘hot’ biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. 68Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration. PMID:26583314

  11. Aryl- and heteroaryl-thiosemicarbazone derivatives and their metal complexes: a pharmacological template.

    PubMed

    Moorthy, Narayana S H N; Cerqueira, Nuno M F S A; Ramos, Maria J; Fernandes, Pedro A

    2013-05-01

    In this review, we discuss the current patents concerning aryl/heteroaryl thiosemicarbazone derivatives as regards to their activities and properties, including coordination (chelation) properties. The mode of action of the aryl/heteroaryl thiosemicarbazone derivatives involves metal coordination with proteins or biological fluids that have metal ions in their structure. Additionally, these molecules can also form multiple hydrogen bonds through their (thio) amide and N3 nitrogen that ensure a strong interaction with the receptor. In some cases, strong π-π interactions can be observed too. Special attention is given to pyridyl, bis-pyridyl, benzoylpyridyl and isatin thiosemicarbazone derivatives that exhibit significant anticancer, antiviral and other activities in free and in metal complexed forms. This key biological role is often related with their capability to inhibit the enzyme ribonucleotide reductase, similar to what is observed with potent anticancer drugs such as Triapine and methisazone. Recent studies have revealed that thiosemicarbazone can also inhibit topoisomerase II α enzyme. Thiosemicarbazone derivatives form coordination complex with various metals such as Zn, Cu, Fe, Co, Ni, Pt, Pd, etc., and these complexes provide better activities than the free thiosemicarbazones. Recent patents show that the controlled or sustained release dosage form of the thiosemicarbazone derivatives along with ionizing radiations is used for the treatment of proliferative diseases (US20110152281, US20110245304, US20120172217). PMID:22963201

  12. Coordination of Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II), Pd(II) and Pt(II) with 2,5-hexanedione bis(thiosemicarbazone), HBTS: crystal structure of cis-[Pd(HBTS)]Cl2 and 1-(2,5-dimethyl-1H-pyrrol-yl)-thiourea.

    PubMed

    Jeragh, Bakir; El-Asmy, Ahmed A

    2014-09-15

    Metal complexes of Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Pd2+ or Pt2+ with 2,5-hexanedione bis(thiosemicarbazone), HBTS; have been prepared and spectroscopically investigated. The empirical formulae of the complexes were suggested based on the elemental analysis. Single crystal of Pd(II) has been solved to be cis-form of square-planar geometry by the X-ray crystallography. 1H and 13C NMR spectra have been recorded for HBTS, Zn(II), Cd(II), Hg(II), Pd(II) and Pt(II) complexes, in DMSO-d6, showing the mode of chelation. The ligand acts as a neutral or a binegative tetradentate (N2S2) or neutral bidentate on the basis of FT-IR. The magnetic moments and electronic spectra provide information about the geometry of the complexes which supported by calculating the ligand field parameters for the Co(II) and Fe(III) complexes. The Ni(II) complex has subnormal magnetic moment (0.71 BM) indicative of a mixed stereochemistry of square-planar and tetrahedral structure. [Cu(HBTS-2H)] measured 0.93 BM indicating high interaction between the copper centers. The ligand may be ordered at the top of the spectrochemical series which giving high ligand field splitting energy (10 Dq=17,900 cm(-1) for Co2+ complex). The mass spectra of some complexes proved their stable chemical formulae while the TGA depicts the degradation steps and the final residue. In evaporating the mother liquor during the preparation of HBTS, new compound is obtained naming 1-(2,5-dimethyl-1H-pyrrol-yl)thiourea and its crystal was solved. PMID:24813284

  13. Coordination of Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II), Pd(II) and Pt(II) with 2,5-hexanedione bis(thiosemicarbazone), HBTS: Crystal structure of cis-[Pd(HBTS)]Cl2 and 1-(2,5-dimethyl-1H-pyrrol-yl)-thiourea

    NASA Astrophysics Data System (ADS)

    Jeragh, Bakir; El-Asmy, Ahmed A.

    2014-09-01

    Metal complexes of Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Pd2+ or Pt2+ with 2,5-hexanedione bis(thiosemicarbazone), HBTS; have been prepared and spectroscopically investigated. The empirical formulae of the complexes were suggested based on the elemental analysis. Single crystal of Pd(II) has been solved to be cis-form of square-planar geometry by the X-ray crystallography. 1H and 13C NMR spectra have been recorded for HBTS, Zn(II), Cd(II), Hg(II), Pd(II) and Pt(II) complexes, in DMSO-d6, showing the mode of chelation. The ligand acts as a neutral or a binegative tetradentate (N2S2) or neutral bidentate on the basis of FT-IR. The magnetic moments and electronic spectra provide information about the geometry of the complexes which supported by calculating the ligand field parameters for the Co(II) and Fe(III) complexes. The Ni(II) complex has subnormal magnetic moment (0.71 BM) indicative of a mixed stereochemistry of square-planar and tetrahedral structure. [Cu(HBTS-2H)] measured 0.93 BM indicating high interaction between the copper centers. The ligand may be ordered at the top of the spectrochemical series which giving high ligand field splitting energy (10Dq = 17,900 cm-1 for Co2+ complex). The mass spectra of some complexes proved their stable chemical formulae while the TGA depicts the degradation steps and the final residue. In evaporating the mother liquor during the preparation of HBTS, new compound is obtained naming 1-(2,5-dimethyl-1H-pyrrol-yl)thiourea and its crystal was solved.

  14. QSAR Studies of Copper Azamacrocycles and Thiosemicarbazones

    PubMed Central

    Wolohan, Peter; Yoo, Jeongsoo; Welch, Michael J.; Reichert, David E.

    2008-01-01

    Genetic algorithms (GA) were used to develop specific copper metal-ligand force field parameters for the MM3 force field, from a combination of crystallographic structures and ab initio calculations. These new parameters produced results in good agreement with experiment and previously reported copper metal-ligand parameters for the AMBER force field. The MM3 parameters were then used to develop several Quantitative Structure Activity Relationship (QSAR) models. A successful QSAR for predicting the lipophilicity (logPow) of several classes of Cu(II) chelating ligands, was built using a training set of thirty-two Cu(II) radiometal complexes and six simple molecular descriptors. The QSAR exhibited a correlation between the predicted and experimental logPow with a r2 = 0.95, q2 = 0.92. When applied to an external test set of eleven Cu(II) complexes the QSAR preformed with great accuracy; r2 = 0.93 and a q2 = 0.91 utilizing a leave-one-out cross-validation analysis. Additional QSAR models were developed to predict the biodistribution of a smaller set of Cu(II) bis(thiosemicarbazone) complexes. PMID:16107156

  15. Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

    PubMed Central

    Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

    2013-01-01

    The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

  16. Synthesis, structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands.

    PubMed

    Kasuga, Noriko Chikaraishi; Sekino, Kiyoshi; Ishikawa, Motoki; Honda, Ayano; Yokoyama, Masaki; Nakano, Saori; Shimada, Nobuhiro; Koumo, Chisa; Nomiya, Kenji

    2003-08-01

    ,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes. PMID:12888265

  17. Ferromagnetism in Cu 3-thiosemicarbazone- 2,3-dioxoindole complexes

    NASA Astrophysics Data System (ADS)

    Zentková, M.; Kováč, J.; Zentko, A.; Košturiak, A.

    1991-12-01

    We report evidence for ferromagnetic ordering in Cu-chelates of 3-thiosemicarbazone-2,3-dioxoindole (isatine). It has been found that the Curie temperature is 16.8 K and is independent of the Cu content.

  18. Management of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone-induced methemoglobinemia

    PubMed Central

    Kunos, Charles A; Radivoyevitch, Tomas; Ingalls, Stephen T; Hoppel, Charles L

    2012-01-01

    The anticancer agent 3-aminopyridine-2-carboxaldehyde thiosemicarbazone is a ribonucleotide reductase inhibitor. It inactivates ribonucleotide reductase by disrupting an iron-stabilized radical in ribonucleotide reductase's small subunits, M2 and M2b (p53R2). Unfortunately, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone also alters iron II (Fe2+) in hemoglobin. This creates Fe3+ methemoglobin that does not deliver oxygen. Fe2+ in hemoglobin normally auto-oxidizes to inactive Fe3+ methemoglobin at a rate of nearly 3% per day and this is counterbalanced by a reductase system that normally limits methemoglobin concentrations to less than 1% of hemoglobin. This balance may be perturbed by symptomatic toxicity levels during 3-aminopyridine-2-carboxaldehyde thiosemicarbazone therapy. Indications of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone sequelae attributable to methemoglobinemia include resting dyspnea, headaches and altered cognition. Management of methemoglobinemia includes supplemental oxygen, ascorbate and, most importantly, intravenously administered methylene blue as a therapeutic antidote. PMID:22335579

  19. Synthesis, Characterization, and In Vitro Cytotoxic Activities of Benzaldehyde Thiosemicarbazone Derivatives and Their Palladium (II) and Platinum (II) Complexes against Various Human Tumor Cell Lines

    PubMed Central

    Hernándeza, Wilfredo; Paz, Juan; Vaisberg, Abraham; Spodine, Evgenia; Richter, Rainer; Beyer, Lothar

    2008-01-01

    The palladium (II) bis-chelate Pd (L1−3)2 and platinum (II) tetranuclear Pt4(L4)4 complexes of benzaldehyde thiosemicarbazone derivatives have been synthesized, and characterized by elemental analysis and IR, FAB(+)-mass and NMR (1H, 13C) spectroscopy. The complex Pd(L2)2 [HL2 = m-CN-benzaldehyde thiosemicarbazone] shows a square-planar geometry with two deprotonated ligands (L) coordinated to PdII through the nitrogen and sulphur atoms in a transarrangement, while the complex Pt4(L4)4 [HL4 = 4-phenyl-1-benzaldehyde thiosemicarbazone] has a tetranuclear geometry with four tridentate ligands coordinated to four PtII ions through the carbon (aromatic ring), nitrogen, and sulphur atoms where the ligands are deprotonated at the NH group. The in vitro antitumor activity of the ligands and their complexes was determined against different human tumor cell lines, which revealed that the palladium (II) and platinum (II) complexes are more cytotoxic than their ligands with IC50 values at the range of 0.07–3.67 μM. The tetranuclear complex Pt4(L4)4, with the phenyl group in the terminal amine of the ligand, showed higher antiproliferative activity (CI50 = 0.07–0.12 μM) than the other tested palladium (II) complexes. PMID:19148285

  20. Interaction of Triapine and related thiosemicarbazones with iron(III)/(II) and gallium(III): a comparative solution equilibrium study†

    PubMed Central

    Enyedy, Éva A.; Primik, Michael F.; Kowol, Christian R.; Arion, Vladimir B.; Kiss, Tamás; Keppler, Bernhard K.

    2012-01-01

    Stoichiometry and stability of GaIII, FeIII, FeII complexes of Triapine and five related α-N heterocyclic thiosemicarbazones with potential antitumor activity have been determined by pH-potentiometry, UV-vis spectrophotometry, 1H NMR spectroscopy, and spectrofluorimetry in aqueous solution (with 30% DMSO), together with the characterization of the proton dissociation processes. Additionally, the redox properties of the iron complexes were studied by cyclic voltammetry at various pH values. Formation of high stability bis-ligand complexes was found in all cases, which are predominant at physiological pH with FeIII/FeII, whilst only at the acidic pH range with GaIII. The results show that among the thiosemicarbazones with various substituents the N-terminal dimethylation does not exert a measurable effect on the redox potential, but has the highest impact on the stability of the complexes as well as the cytotoxicity, especially in the absence of a pyridine-NH2 group in the molecule. In addition the fluorescence properties of the ligands in aqueous solution and their changes caused by GaIII were studied. PMID:21523301

  1. Trypanotoxic activity of thiosemicarbazone iron chelators.

    PubMed

    Ellis, Samuel; Sexton, Darren W; Steverding, Dietmar

    2015-03-01

    Only a few drugs are available for treating sleeping sickness and nagana disease; parasitic infections caused by protozoans of the genus Trypanosoma in sub-Saharan Africa. There is an urgent need for the development of new medicines for chemotherapy of these devastating diseases. In this study, three newly designed thiosemicarbazone iron chelators, TSC24, Dp44mT and 3-AP, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL-60 cells. In addition to their iron chelating properties, TSC24 and Dp44mT inhibit topoisomerase IIα while 3-AP inactivates ribonucleotide reductase. All three compounds exhibited anti-trypanosomal activity, with minimum inhibitory concentration (MIC) values ranging between 1 and 100 µM and 50% growth inhibition (GI50) values of around 250 nM. Although the compounds did not kill HL-60 cells (MIC values >100 µM), TSC24 and Dp44mT displayed considerable cytotoxicity based on their GI50 values. Iron supplementation partly reversed the trypanotoxic and cytotoxic activity of TSC24 and Dp44mT but not of 3-AP. This finding suggests possible synergy between the iron chelating and topoisomerase IIα inhibiting activity of the compounds. However, further investigation using separate agents, the iron chelator deferoxamine and the topoisomerase II inhibitor epirubicin, did not support any synergy for the interaction of iron chelation and topoisomerase II inhibition. Furthermore, TSC24 was shown to induce DNA degradation in bloodstream forms of T. brucei indicating that the mechanism of trypanotoxic activity of the compound is topoisomerase II independent. In conclusion, the data support further investigation of thiosemicarbazone iron chelators with dual activity as lead compounds for anti-trypanosomal drug development. PMID:25595343

  2. Methemoglobin formation by triapine, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), and other anticancer thiosemicarbazones: identification of novel thiosemicarbazones and therapeutics that prevent this effect.

    PubMed

    Quach, Patricia; Gutierrez, Elaine; Basha, Maram Talal; Kalinowski, Danuta S; Sharpe, Philip C; Lovejoy, David B; Bernhardt, Paul V; Jansson, Patric J; Richardson, Des R

    2012-07-01

    Thiosemicarbazones are a group of compounds that have received comprehensive investigation as anticancer agents. The antitumor activity of the thiosemicarbazone, 3-amino-2-pyridinecarboxaldehyde thiosemicarbazone (3-AP; triapine), has been extensively assessed in more than 20 phase I and II clinical trials. These studies have demonstrated that 3-AP induces methemoglobin (metHb) formation and hypoxia in patients, limiting its usefulness. Considering this problem, we assessed the mechanism of metHb formation by 3-AP compared with that of more recently developed thiosemicarbazones, including di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT). This was investigated using intact red blood cells (RBCs), RBC lysates, purified oxyhemoglobin, and a mouse model. The chelation of cellular labile iron with the formation of a redox-active thiosemicarbazone-iron complex was found to be crucial for oxyhemoglobin oxidation. This observation was substantiated using a thiosemicarbazone that cannot ligate iron and also by using the chelator, desferrioxamine, that forms a redox-inactive iron complex. Of significance, cellular copper chelation was not important for metHb generation in contrast to its role in preventing tumor cell proliferation. Administration of Dp44mT to mice catalyzed metHb and cardiac metmyoglobin formation. However, ascorbic acid administered together with the drug in vivo significantly decreased metHb levels, providing a potential therapeutic intervention. Moreover, we demonstrated that the structure of the thiosemicarbazone is of importance in terms of metHb generation, because the DpT analog, di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), does not induce metHb generation in vivo. Hence, DpC represents a next-generation thiosemicarbazone that possesses markedly superior properties. This investigation is important for developing more effective thiosemicarbazone treatment regimens. PMID:22508546

  3. [Study of the effect of thiosemicarbazones against Toxoplasma gondii].

    PubMed

    Gomes, Marco Antônio G B; Carreira, Gabriela M; Souza, Daniela P V; Nogueira, Paulo Marcos R; de Melo, Edésio J T; Maria, Edmilson J

    2013-04-01

    Toxoplasmosis is a neglected disease, with an estimated occurrence of one-third of the population worldwide. Research in medicinal chemistry has for some years been pursuing the development of new drugs against toxoplasmosis, because current treatments cause serious side effects in the patient. The use of thiosemicarbazones as an alternative option for the treatment of various diseases has been published in recent years, due to their, among others, anticancer, antimalarial, antitrypanosomal, antibacterial, and antitoxoplasmosis activities, the latter being the subject of this study, which is based upon biological analyses and tests of the response of Toxoplasma gondii in the presence of thiosemicarbazones. PMID:23849723

  4. Organometallic ruthenium complexes with thiosemicarbazone ligands: Synthesis, structure and cytotoxicity of [(η6-p-cymene)Ru(NS)Cl]+ (NS = 9-anthraldehyde thiosemicarbazones)

    PubMed Central

    Beckford, Floyd A.; Leblanc, Gabriel; Thessing, Jeffrey; Shaloski, Michael; Frost, Brian J.; Li, Liya; Seeram, Navindra P.

    2009-01-01

    A series of half-sandwich arene-ruthenium complexes of the type [(η6-p-cymene) Ru(thiosemicarbazone)Cl]+ have been synthesized and their biological activity investigated. The first structurally characterized arene-ruthenium half-sandwich complex with a thiosemicarbazone ligand is reported. PMID:20160909

  5. Improved cytotoxicity of pyridyl-substituted thiosemicarbazones against MCF-7 when used as metal ionophores.

    PubMed

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2016-02-01

    Zinc is the second most abundant transition metal in the human body, between 3 and 10% of human genes encoding for zinc binding proteins. We have investigated the interplay of reactive oxygen species and zinc homeostasis on the cytotoxicity of the thiosemicarbazone chelators against the MCF-7 cell line. The cytotoxicity of thiosemicarbazone chelators against MCF-7 can be improved through supplementation of ionic zinc provided the zinc ion is at a level exceeding the thiosemicarbazone concentration. Elimination of the entire cell population can be accomplished with this regime, unlike the plateau of cytotoxicity observed on thiosemicarbazone monotherapy. The cytotoxic effects of copper complexes of the thiosemicarbazone are not enhanced by zinc supplementation, displacement of copper from the complex being disfavoured. Treatment of MCF-7 with uncomplexed thiosemicarbazone initiates post G1 blockade alongside the induction of apoptosis, cell death being abrogated through subsequent supplementation with zinc ion after drug removal. This would implicate a metal depletion mechanism in the cytotoxic effect of the un-coordinated thiosemicarbazone. The metal complexes of the species, however, fail to initiate similar G1 blockade and apparently exert their cytotoxic effect through generation of reactive oxygen species, suggesting that multiple mechanisms of cytotoxicity can be associated with the thiosemicarbazones dependant on the level of metal ion association. PMID:26683314

  6. Vibrational spectra of palladium 5-nitrofuryl thiosemicarbazone complexes: Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Gambino, Dinorah; Otero, Lucía; Vieites, Marisol; Boiani, Mariana; González, Mercedes; Baran, Enrique J.; Cerecetto, Hugo

    2007-10-01

    The vibrational spectroscopic behavior of a series of 16 palladium(II) complexes with 8 bioactive nitrofuran containing thiosemicarbazones as ligands has been studied in the solid state. The IR and Raman spectra of these complexes and the free nitrofuran thiosemicarbazone ligands were recorded and analyzed. Experimental spectra were satisfactorily described by density functional theory (DFT) calculations. The combination of experimental and theoretical methods allowed us to perform the characterization of the main vibrations that show the mode of coordination of the thiosemicarbazone moiety to palladium even though these vibration bands are located in spectral regions showing a complicated pattern due to the presence of vibrations of the nitrofuran moiety and combination modes involving furan vibrations. A characteristic vibrational spectroscopic pattern has been defined for Pd(II) 5-nitrofuryl thiosemicarbazone complexes. This systematic knowledge may be useful for the analysis of the spectroscopic behavior of other coordination compounds holding the 5-nitrofuran thiosemicarbazone moiety.

  7. Cytotoxic behavior and spectroscopic characterization of metal complexes of ethylacetoacetate bis(thiosemicarbazone) ligand.

    PubMed

    El-Tabl, Abdou Saad; El-wahed, Moshira Mohamed Abd; Rezk, Ahmed Mahmoud Salah Mahmoud

    2014-01-01

    Reaction of Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ion with 2,4-dihydrazino-thioamido-1-ethoxybutane led to the formation of mono and binuclear complexes. These complexes have been characterized by elemental analyses, IR, UV-Vis spectra, magnetic moments, molar conductances, (1)H NMR and mass spectra (ligand and its Zn(II) complex), thermal analyses (DTA and TGA) and ESR measurements. The IR data suggest the involvement of sulfur and azomethane nitrogen atoms in coordination to the central metal ion .The Molar conductances of the complexes in DMF are commensurate with their non-ionic character. The ESR spectra of Cu(II) complexes show axial type symmetry (d(x2-y2)) ground state with covalent bond character. On the basis of spectral studies, octahedral or tetrahedral geometry has been assigned to the metal complexes. Complexes have been tested invitro against tumor cells and number of microorganisms in order to assess their antitumor and antimicrobial properties. PMID:24011929

  8. Cytotoxic behavior and spectroscopic characterization of metal complexes of ethylacetoacetate bis(thiosemicarbazone) ligand

    NASA Astrophysics Data System (ADS)

    El-Tabl, Abdou Saad; El-wahed, Moshira Mohamed Abd; Rezk, Ahmed Mahmoud Salah Mahmoud

    2014-01-01

    Reaction of Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ion with 2,4-dihydrazino-thioamido-1-ethoxybutane led to the formation of mono and binuclear complexes. These complexes have been characterized by elemental analyses, IR, UV-Vis spectra, magnetic moments, molar conductances, 1H NMR and mass spectra (ligand and its Zn(II) complex), thermal analyses (DTA and TGA) and ESR measurements. The IR data suggest the involvement of sulfur and azomethane nitrogen atoms in coordination to the central metal ion .The Molar conductances of the complexes in DMF are commensurate with their non-ionic character. The ESR spectra of Cu(II) complexes show axial type symmetry (d(x2-y2)) ground state with covalent bond character. On the basis of spectral studies, octahedral or tetrahedral geometry has been assigned to the metal complexes. Complexes have been tested invitro against tumor cells and number of microorganisms in order to assess their antitumor and antimicrobial properties.

  9. Crystal structures of copper(II) complexes of 2-formylpyridine substituted thiosemicarbazones; the first example of a coordinated thiosemicarbazone with a thiol function

    NASA Astrophysics Data System (ADS)

    West, D. X.; Swearingen, J. K.; Romack, T. J.; Billeh, I. S.; Jasinski, J. P.; Li, Y.; Staples, R. J.

    2001-08-01

    The crystal structures of two 5-coordinate copper(II) complexes containing neutral, tridentate 2-formylpyridine N(4)-substituted thiosemicarbazones have been determined. 2-Formylpyridine N(4)-cyclohexylthiosemicarbazone, HFo4CHex coordinates via the pyridine nitrogen, imine nitrogen and thione sulfur with two chloro ligands to produce [Cu(HFo4CHex)Cl 2]. Similarly, 2-formylpyridine 3-(4-methylpiperazine)thiosemicarbazone, HFoppz4M, produces [Cu(HFoppz4M)Cl 2] with one major difference; rather than the expected thione form of the thiosemicarbazone moiety, it coordinates as the thiol isomer. Both complexes are close to a square pyramid structure with axial and equatorial chloro ligands and the thiosemicarbazone moieties of both ligands nearly planar. Also included is the crystal structure of N-cyclohexylthiosemicarbazide, CHextsc.

  10. Bis(thiosemicarbazonato) chelates of Co(II), Ni(II), Cu(II), Pd(II) and Pt(II)

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Singh, R.

    1985-01-01

    Bis chelates of Co(II), Ni(II), Cu(II), Pd(II) and Pt(II) with the enolic form of diethyl ketone and methyl n-propyl thiosemicarbazones were synthesized and characterized by elemental analyses, magnetic moments, i.r. and electronic and electron spin resonance spectral studies. All the complexes were found to have the composition ML 2 [where M = Co(II), Ni(II), Cu(II), Pd(ii) and Pt(II) and L = thiosemicarbazones of diethyl ketone and methyl n-propyl ketone]. Co(II) and Cu(II) complexes are paramagnetic and may have polymeric six-coordinate octahedral and square planar geometries, respectively. The Ni(II), Pd(II) and Pt(II) complexes are diamagnetic and may have square planar geometries. Pyridine adducts (ML 2·2Py) of Ni(II) and Cu(II) complexes were also prepared and characterized.

  11. Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors.

    PubMed

    Zhu, Tian-Hua; Cao, Shu-Wen; Yu, Yan-Ying

    2013-11-01

    A series of hydroxy- and methoxy-substituted paeonol thiosemicarbazone analogues were synthesized as potential tyrosinase inhibitors and their inhibitory effects on mushroom tyrosinase and inhibitory mechanism were evaluated. Paeonol thiosemicarbazone analogues have been found exhibiting more remarkable inhibition than their indexcompounds on mushroom tyrosinase. Among them, compound 2,4-dihydroxy acetophenone-4-phenyl-3-thiosemicarbazone (d1) had the most potent inhibition activity with the IC50 value of 0.006 ± 0.001 mM, displayed as a reversible competitive inhibitor. The inhibitory ability of o- or p-substituted acetophenone thiosemicarbazones was: di-substituted acetophenone thiosemicarbazones>mono-substituted acetophenone thiosemicarbazones>non-substituted acetophenone thiosemicarbazones. Copper ions chelation assay explained that compound d1 exhibited competitive inhibition by forming a chelate with the copper ions at the catalytic domain of tyrosinase as well as indicate a 1.5:1 binding ratio of compound d1 with copper ions. In the fluorescence spectrum study, compound d1 behaved stronger fluorescence quenching on tyrosinase towards d1-Cu(2+) complex, inhibiting tyrosinase mainly by means of chelating the two copper ions in the active site. The newly synthesized compounds may serve as structural templates for designing and developing novel tyrosinase inhibitors. PMID:24120880

  12. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

    PubMed Central

    Souza, Marina Azevêdo; Johann, Susana; Lima, Luciana Alves Rodrigues dos Santos; Campos, Fernanda Fraga; Mendes, Isolda Castro; Beraldo, Heloisa; de Souza-Fagundes, Elaine Maria; Cisalpino, Patrícia Silva; Rosa, Carlos Augusto; Alves, Tânia Maria de Almeida; de Sá, Nívea Pereira; Zani, Carlos Leomar

    2013-01-01

    Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes. PMID:23778660

  13. Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies

    NASA Astrophysics Data System (ADS)

    Haribabu, J.; Subhashree, G. R.; Saranya, S.; Gomathi, K.; Karvembu, R.; Gayathri, D.

    2016-04-01

    A new series of isatin based thiosemicarbazones has been synthesized from benzylisatin and unsubstituted/substituted thiosemicarbazides (1-5). The synthesized compounds were characterized by elemental analyses, and UV-Visible, FT-IR, 1H &13C NMR and mass spectroscopic techniques. Three dimensional molecular structure of three compounds (1, 3 and 4) was determined by single crystal X-ray crystallography. Anti-oxidant activity of the thiosemicarbazone derivatives showed their excellent scavenging effect against free radicals. In addition, all the compounds showed good anti-haemolytic activity. In silico molecular docking studies were performed to screen the anti-inflammatory and anti-tuberculosis properties of thiosemicarbazone derivatives.

  14. ESR, electrochemical and reactivity studies of antitrypanosomal palladium thiosemicarbazone complexes

    NASA Astrophysics Data System (ADS)

    Otero, Lucía; Folch, Christian; Barriga, Germán; Rigol, Carolina; Opazo, Lucia; Vieites, Marisol; Gambino, Dinorah; Cerecetto, Hugo; Norambuena, Ester; Olea-Azar, Claudio

    2008-08-01

    Cyclic voltammetry (CV) and electron spin resonance (ESR) techniques were used in the investigation of novel palladium complexes with bioactive thiosemicarbazones derived from 5-nitrofurane or 5-nitrofurylacroleine. Sixteen palladium complexes grouped in two series of the formula [PdCl 2HL] or [PdL 2] were studied. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. The ESR spectra showed two different hyperfine patterns. The stoichiometry of the complexes does not seem to affect significantly the hyperfine constants however we observed great differences between 5-nitrofurane and 5-nitrofurylacroleine derivatives. The scavenger properties of this family of compounds were lower than Trolox.

  15. Reinvestigation of growth of urea thiosemicarbazone monohydrate crystal

    NASA Astrophysics Data System (ADS)

    Srinivasan, Bikshandarkoil R.; Raghavaiah, Pallepogu; Nadkarni, V. S.

    2013-08-01

    The reaction of urea with thiosemicarbazide in 1:1 mole ratio in aqueous solution does not result in the formation of urea thiosemicarbazone monohydrate crystal, as reported by Hanumantharao, Kalainathan and Bhagavannarayana [Spectrochim. Acta A91 (2012) 345-351]. A reinvestigation of the reported reaction reveals that the crystal obtained is the starting material namely thiosemicarbazide, which has been unambiguously confirmed with the aid of infrared and 1H NMR spectra and single crystal X-ray structure determination. Analysis of 1H NMR spectrum reveals that thiosemicarbazide exhibits thione-thiol tautomerism in solution. In contrast, thiosemicarbazide exists as the thione tautomer in the solid state.

  16. Structural studies of six and four coordinate zinc(II), nickel(II) and dioxovanadium(V) complexes with thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Sreekanth, A.; Sivakumar, S.; Prathapachandra Kurup, M. R.

    2003-07-01

    Three Zn(II) complexes of di-2-pyridyl ketone thiosemicarbazone, an octahedral Ni(II) complex of 2-acetylpyridine hexamethyleneiminyl-3-thiosemicarbazone, and a V(V) complex of 2-acetylpyridine morpholyl-3-thiosemicarbazone were prepared and characterized. Crystal structure of Ni(II) and V(V) complexes are reported. The ligand in the nickel complex is found to coordinate in the thione form with a pseudo octahedral geometry and the vanadium(V) complex has trigonal bipyramidal geometry.

  17. A spectral study of 2-formylimidazole 4N-substituted thiosemicarbazones and their copper(II) complexes

    NASA Astrophysics Data System (ADS)

    West, Douglas X.; Lockwood, Mark A.; Albert, Julyan N.; Liberta, Anthony E.

    1993-11-01

    Copper(II) complexes of 2-formylimidazole 4N-methyl-, 4N-dimethyl- 4N-ethyl- and 3-hexa-methyleneiminylthiosemicarbazone, along with two nickel(II) complexes of the latter thiosemicarbazone, have been synthesized. Infrared, electronic, NMR and ESR spectra have been used to characterize the complexes and the uncomplexed thiosemicarbazones. None of the complexes or thiosemicarbazones possess growth inhibitory activity against Aspergillus niger and Paecilomyces variotii.

  18. Influence of anthraquinone scaffold on E/Z isomer distribution of two thiosemicarbazone derivatives. 2D NMR and DFT studies

    NASA Astrophysics Data System (ADS)

    Marković, Violeta; Joksović, Milan D.; Marković, Svetlana; Jakovljević, Ivan

    2014-01-01

    A distribution of possible isomeric and tautomeric forms of two tautomerizable anthraquinone-thiosemicarbazones with pronounced cytotoxic potential was investigated using 2D NMR and DFT studies. Conformational analysis of the E and Z isomers of both thiosemicarbazones was performed to find out the most stable conformation for each molecule. It was found that superior stability of E-isomers results from ten-membered intramolecular hydrogen bond between thiosemicarbazone N2H and anthraquinone carbonyl group. This hydrogen bond is stronger than that between thiosemicarbazone N2H and ester oxygen, owing to the large partial negative charge on the anthraquinone oxygen.

  19. Ruthenium(II) complexes of 2-benzoylpyridine-derived thiosemicarbazones with cytotoxic activity against human tumor cell lines

    NASA Astrophysics Data System (ADS)

    Graminha, Angelica E.; Rodrigues, Cláudia; Batista, Alzir A.; Teixeira, Letícia R.; Fagundes, Elaine S.; Beraldo, Heloisa

    2008-04-01

    Reaction of [RuCl 3(dppb)H 2O] (dppb = 1,4 bis(diphenylphospine)butane) with 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N(4)-methyl (H2Bz4M) and N(4)-phehyl (H2Bz4Ph) derivatives gave [RuCl(dppb)(H2Bz4DH)]Cl ( 1), [RuCl(dppb)(H2Bz4M)]Cl ( 2) and [RuCl(dppb)(H2Bz4Ph)]Cl ( 3). The cytotoxic activity of the studied compounds was tested against the MCF-7, TK-10 and UACC-62 human tumor cell lines. The precursor [RuCl 3(dppb)H 2O] exhibits cytocidal activity against the tree cell lines. H2BzDH, H2Bz4M, and [RuCl(dppb)(H2Bz4M)]Cl ( 2) show a selective cytocidal effect against the UACC-62 cell line which makes them the most promising compounds.

  20. Cyclopalladated organosilane-tethered thiosemicarbazones: novel strategies for improving antiplasmodial activity.

    PubMed

    Adams, Muneebah; Barnard, Linley; de Kock, Carmen; Smith, Peter J; Wiesner, Lubbe; Chibale, Kelly; Smith, Gregory S

    2016-04-01

    Two series of ferrocenyl- and aryl-derived cyclopalladated organosilane thiosemicarbazone complexes were synthesised via C-H bond activation. Selected compounds were evaluated for in vitro antiplasmodial activity against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the human malaria parasite Plasmodium falciparum. Cyclopalladation of the thiosemicarbazones resulted in antiplasmodial activities in the low micromolar range. PMID:26911403

  1. The structure-activity relationships of the antiviral chemotherapeutic activity of isatin β-thiosemicarbazone

    PubMed Central

    Bauer, D. J.; Sadler, P. W.

    1960-01-01

    As part of an investigation devoted to the development of new antiviral agents a compound of established antiviral activity has been subjected to systematic structural modification. The structure-activity data so obtained have been used in the design of new compounds, some of which are described. The compound chosen was isatin β-thiosemicarbazone, which has high activity against neurovaccinia infection in mice, and a 4-point parallel-line assay of in vivo chemotherapeutic activity has been developed, which has enabled the activity of the derivatives to be determined against isatin β-thiosemicarbazone as a standard. The overall dimensions of the isatin β-thiosemicarbazone molecule appear to be nearly maximal for the retention of high activity, as all substituents in the aromatic ring decrease the activity irrespective of their nature or position. The projection of the -CS.NH2 group in relation to the ring nitrogen was found to be critical, as the α-thiosemicarbazone was inactive. A number of modifications of the side-chain were investigated:all led to reduction or loss of antiviral activity. The antiviral activity showed a positive correlation with chloroform solubility over a considerable range. The most active compound encountered was 1-ethylisatin β-thiosemicarbazone, with an activity of 286 (isatin β-thiosemicarbazone≡100). Isatin β-thiosemicarbazone showed no activity against 15 other viruses, and 20 related compounds showed on activity against ectromelia. PMID:13797622

  2. Transition metal quinone-thiosemicarbazone complexes 3: Spectroscopic characterizations of spin-mixed iron (III) of naphthoquinone-thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Chikate, Rajeev C.; Padhye, Subhash B.

    2007-04-01

    An interesting series of iron (III) complexes with naphthoquinone-thiosemicarbazones are synthesized and physico-chemically characterized by elemental analysis, UV-vis, IR, EPR and magnetic susceptibility measurements. They possess a cationic octahedral [FeL 2] + species and a tetrahedral [FeCl 4] - anion and exhibit unusual spin-mixed states involving high-spin and low-spin ferric centers as revealed from magnetic behavior with significant amount of exchange interactions mediated by intermolecular associations. The magnetic susceptibility data is fitted with S=5/2 and S=1/2 Heisengberg's exchange coupled model; Hˆ=-2JSS and the magnetic exchange interactions are found to be of the order of -13.6 cm -1 indicating the moderate coupling between two paramagnetic centers present in different chemical and structural environment. The presence of spin-paired iron (III) cation having dxz2dxz2dxz1 ground state is revealed from the EPR spectra with three prominent peaks while the high-spin tetrahedral iron (III) anion exhibits characteristics g = 4 signal whose intensity increases with lowering the temperature suggesting its influence on the magnetic properties of the complex molecule. FTIR measurements indicate tridentate ONS donor systems involving quinone/hydroxyl oxygen, imine/hydrazinic nitrogen and thione/thiol sulfur atoms as binding sites for naphthoquinone-thiosemicarbazones.

  3. Synthesis, Spectroscopic, and Antimicrobial Studies on Bivalent Nickel and Copper Complexes of Bis(thiosemicrbazone)

    PubMed Central

    Chandra, Sulekh; Raizada, Smriti; Tyagi, Monika; Gautam, Archana

    2007-01-01

    A series of metal complexes of Cu(II) and Ni(II) having the general composition [M(L)X2] with benzil bis(thiosemicarbazone) has been prepared and characterized by element chemical analysis, molar conductance, magnetic susceptibility measurements, and spectral (electronic, IR, EPR, mass) studies. The IR spectral data suggest the involvement of sulphur and azomethane nitrogen in coordination to the central metal ion. On the basis of spectral studies, an octahedral geometry has been assigned for Ni(II) complexes but a tetragonal geometry for Cu(II) complexes. The free ligand and its metal complexes have been tested in vitro against a number of microorganisms in order to assess their antimicrobial properties. PMID:18273385

  4. Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging.

    PubMed

    Cortezon-Tamarit, Fernando; Sarpaki, Sophia; Calatayud, David G; Mirabello, Vincenzo; Pascu, Sofia I

    2016-06-01

    The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using (64) CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21(st) century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in "cold" and "hot" Cu(II) and Ga(III) derivatives for PET applications and (111) In(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications. PMID:27149900

  5. Spectral, thermal, electrochemical and analytical studies on Cd(II) and Hg(II) thiosemicarbazone complexes

    NASA Astrophysics Data System (ADS)

    El-Asmy, A. A.; El-Gammal, O. A.; Saleh, H. S.

    2008-11-01

    The coordination characteristic of the investigated thiosemicarbazones towards hazard pollutants, Cd(II) and Hg(II), becomes the first goal. Their complexes have been studied by microanalysis, thermal, electrochemical and spectral (electronic, IR and MS) studies. The substitutent (salicylaldehyde, acetophenone, benzophenone, o-hydroxy- p-methoxybenzophenone or diacetylmonoxime) plays an important role in the complex formation. The coordination sites were the S for thiosemicarbazide (HTS); NN for benzophenone thiosemicarbazone (HBTS); NS for acetophenone thiosemicarbazone (HATS) and salicylaldehyde thiosemicarbazone (H 2STS); NNS or NSO for diacetylmonoxime thiosemicarbazone (H 2DMTS). The stability constants of Hg(II) complexes were higher than Cd(II). The kinetic and thermodynamic parameters for the different thermal decomposition steps in the complexes have been evaluated. The activation energy values of the first step ordered the complexes as: [Cd(H 2STS)Cl 2]H 2O > [Cd(H 2DAMTS)Cl 2] > [Cd(HBTS) 2Cl 2]2H 2O > [Cd(HATS) 2Cl 2]. The CV of [Cd(H 2STS)Cl 2]H 2O and [Hg(HBTS)Cl 2] were recorded. The use of H 2DMTS as a new reagent for the separation and determination of Cd(II) ions from water and some synthetic samples using flotation technique is aimed to be discussed.

  6. In vitro evaluation of the activity of thiosemicarbazone derivatives against mycotoxigenic fungi affecting cereals.

    PubMed

    Degola, Francesca; Morcia, Caterina; Bisceglie, Franco; Mussi, Francesca; Tumino, Giorgio; Ghizzoni, Roberta; Pelosi, Giorgio; Terzi, Valeria; Buschini, Annamaria; Restivo, Francesco Maria; Lodi, Tiziana

    2015-05-01

    With a steadily increasing world population, a more efficient system of food production is of paramount importance. One of the major causes of food spoilage is the presence of fungal pathogens and the production and accumulation of mycotoxins. In the present work we report a study on the activity of a series of functionalized thiosemicarbazones (namely cuminaldehyde, trans-cinnamaldehyde, quinoline-2-carboxyaldehyde, 5-fluoroisatin thiosemicarbazone and 5-fluoroisatin N(4)-methylthiosemicarbazone), as antifungal and anti-mycotoxin agents, against the two major genera of cereal mycotoxigenic fungi, i.e. Fusarium and Aspergillus. These thiosemicarbazones display different patterns of efficacy on fungal growth and on mycotoxin accumulation depending on the fungal species. Some of the molecules display a greater effect on mycotoxin synthesis than on fungal growth. PMID:25702884

  7. Spectral studies of copper(II) complexes of 6-(3-thienyl) pyridine-2-thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Mahjoub, Omima Abdalla; Farina, Yang

    2014-09-01

    Two novel copper(II) complexes [Cu(HL)Cl]Cl˙H2O (1) and [Cu(L)NO3]˙H2O (2) of the three NNS donor thiosemicarbazone ligand 6-(3-thienyl) pyridine-2-thiosemicarbazone have been synthesized. The ligand and its copper(II) complexes were characterized by elemental analysis (C, H, N, and S), FT-IR, UV-visible, magnetic susceptibility and molar conductance. The thiosemicarbazone is present either as the thione form in complex 1 or as thiol form in complex 2 and is coordinated to copper(II) atom via the pyridine nitrogen atom, the azomethine nitrogen atom and the sulfur atom. The physicochemical and spectral data suggest square planar geometry for copper(II) atoms.

  8. Spectral studies of copper(II) complexes of 6-(3-thienyl) pyridine-2-thiosemicarbazone

    SciTech Connect

    Mahjoub, Omima Abdalla; Farina, Yang

    2014-09-03

    Two novel copper(II) complexes [Cu(HL)Cl]Cl.H{sub 2}O (1) and [Cu(L)NO{sub 3}]Ðœ‡H{sub 2}O (2) of the three NNS donor thiosemicarbazone ligand 6-(3-thienyl) pyridine-2-thiosemicarbazone have been synthesized. The ligand and its copper(II) complexes were characterized by elemental analysis (C, H, N, and S), FT-IR, UV-visible, magnetic susceptibility and molar conductance. The thiosemicarbazone is present either as the thione form in complex 1 or as thiol form in complex 2 and is coordinated to copper(II) atom via the pyridine nitrogen atom, the azomethine nitrogen atom and the sulfur atom. The physicochemical and spectral data suggest square planar geometry for copper(II) atoms.

  9. Spectroscopic evaluation of manganese(II) complexes derived from semicarbazones and thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Gupta, Lokesh Kumar

    2005-09-01

    Manganese(II) complexes having the general composition Mn(L) 2X 2 [where L = isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC) and 4-aminoacetophenone thiosemicarbazone (LLD) and X = Cl -, 1/2SO 42-] have been synthesized. All the complexes were characterized by elemental analyses, molar conductance, magnetic moment susceptibility, EI-mass, 1H NMR, IR, EPR and electronic spectral studies. All the complexes show magnetic moments corresponding to five unpaired electrons. The possible geometries of the complexes were assigned on the basis of EPR, electronic and infrared spectral studies.

  10. EPR, mass, IR, electronic, and magnetic studies on copper(II) complexes of semicarbazones and thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Gupta, Lokesh Kumar

    2005-01-01

    Copper(II) complexes having the general composition Cu(L) 2X 2 [where L = isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC), and 4-aminoacetophenone thiosemicarbazone (LLD) and X = Cl -, 1/2SO 42-] have been synthesized. All the Cu(II) complexes reported here have been characterized by elemental analyses, molar conductance, magnetic moment susceptibility, EI mass, 1H NMR, IR, EPR, and electronic spectral studies. All the complexes were found to have magnetic moments corresponding to one unpaired electrons. The possible geometries of the complexes were assigned on the basis of EPR, electronic, and infrared spectral studies.

  11. Manganese(II) complexes of substituted di-2-pyridyl ketone thiosemicarbazones: Structural and spectral studies

    NASA Astrophysics Data System (ADS)

    Philip, Varughese; Suni, V.; Kurup, Maliyeckal R. Prathapachandra; Nethaji, Munirathinam

    2006-05-01

    The reaction between manganese(II) acetate and two substituted thiosemicarbazones derived from di-2-pyridyl ketone (HL) in 1:2 molar ratio produces new complexes of general formula [MnL 2]. The thiosemicarbazone moiety in HL deprotonates and gets coordinated to Mn(II) through the azomethine nitrogen, one of the pyridyl nitrogens, and the thiolate sulfur in both the complexes. The crystal structure of [ MnL21] was established by single crystal X-ray diffraction and the compound crystallizes into a monoclinic lattice with P2 1/ c space group. Manganese(II) exists in a distorted octahedral geometry in the complexes.

  12. Intermolecular interaction of thiosemicarbazone derivatives to solvents and a potential Aedes aegypti target

    NASA Astrophysics Data System (ADS)

    da Silva, João Bosco P.; Hallwass, Fernando; da Silva, Aluizio G.; Moreira, Diogo Rodrigo; Ramos, Mozart N.; Espíndola, José Wanderlan P.; de Oliveira, Ana Daura T.; Brondani, Dalci José; Leite, Ana Cristina L.; Merz, Kenneth M.

    2015-08-01

    DFT calculations were used to access information about structure, energy and electronic properties of series of phenyl- and phenoxymethyl-(thio)semicarbazone derivatives with demonstrated activity against the larvae of Aedes aegypti in stage L4. The way as the thiosemicarbazone derivatives can interact with solvents like DMSO and water were analyzed from the comparison between calculated and experimental 1H NMR chemical shifts. The evidences of thiosemicarbazone derivatives making H-bond interaction to solvent have provide us insights on how they can interact with a potential A. aegypti's biological target, the Sterol Carrier Protein-2.

  13. A novel series of thiosemicarbazone drugs: from synthesis to structure.

    PubMed

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S; Alsalim, Tahseen A; Ghali, Thaer S; Bolandnazar, Zeinab

    2015-02-25

    A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, (1)H NMR, (13)C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical (13)C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained. PMID:25291504

  14. A novel series of thiosemicarbazone drugs: From synthesis to structure

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S.; Alsalim, Tahseen A.; Ghali, Thaer S.; Bolandnazar, Zeinab

    2015-02-01

    A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

  15. Targeting Iron in Colon Cancer via Glycoconjugation of Thiosemicarbazone Prochelators.

    PubMed

    Akam, Eman A; Tomat, Elisa

    2016-08-17

    The implication of iron in the pathophysiology of colorectal cancer is documented at both the biochemical and epidemiological levels. Iron chelators are therefore useful molecular tools for the study and potential treatment of this type of cancer characterized by high incidence and mortality rates. We report a novel prochelation strategy that utilizes a disulfide redox switch to connect a thiosemicarbazone iron-binding unit with carbohydrate moieties targeting the increased expression of glucose transporters in colorectal cancer cells. We synthesized three glycoconjugates (GA2TC4, G6TC4, and M6TC4) with different connectivity and/or carbohydrate moieties, as well as an aglycone analog (ATC4). The sugar conjugates present increased solubility in neutral aqueous solutions, and the ester-linked conjugates M6TC4 and G6TC4 compete as effectively as d-glucose for transporter-mediated cellular uptake. The glycoconjugates show improved selectivity compared to the aglycone analog and are 6-11 times more toxic in Caco-2 colorectal adenocarcinoma cells than in normal CCD18-co colon fibroblasts. PMID:27471913

  16. Synthesis, spectroscopic studies and crystal structure of ( E)-2-(2,4-dihydroxybenzylidene)thiosemicarbazone and ( E)-2-[(1 H-indol-3-yl)methylene]thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Yıldız, Mustafa; Ünver, Hüseyin; Erdener, Diğdem; Kiraz, Aşkın; İskeleli, Nazan Ocak

    2009-02-01

    Thiosemicarbazone Schiff bases ( 1 and 2) derived from 2,4-dihydroxybenzaldehyde, indoline-3-carbaldehyde and thiosemicarbazone have been synthesized and their structures were elucidated by elemental analysis, FT-IR, 1H NMR, 13C NMR and UV-visible spectroscopic techniques. The structures of compounds 1 and 2 have also been examined cyrstallographically. The title compounds 1 and 2 crystallize in the monoclinic space group C2/ c and triclinic space group P1¯, with unit cell parameters: a = 21.421(1) and 7.233(1), b = 4.131(1) and 11.166(1), c = 24.942(2) and 13.648(1) Å, V = 1856.1(2) and 1019.5(1) Å 3, D x = 1.512 and 1.422 g cm -3 and Z = 8 and 4, respectively.

  17. Anti-HIV activity of thiosemicarbazone and semicarbazone derivatives of (+/-)-3-menthone.

    PubMed

    Mishra, Vibha; Pandeya, S N; Pannecouque, Christophe; Witvrouw, Myriam; De Clercq, E

    2002-05-01

    A series of thiosemicarbazones and semicarbazone derivatives of (+/-)-3-menthone have been synthesized and their anti-HIV activity evaluated against HIV-1(III(B))and HIV-2 (ROD). The studies revealed that maximum protection is offered by chloro-substituted derivatives 2 and 7 against HIV-1 (III(B)) and HIV-2 (ROD). PMID:12210774

  18. The wide pharmacological versatility of semicarbazones, thiosemicarba-zones and their metal complexes.

    PubMed

    Beraldo, Heloisa; Gambino, Dinorah

    2004-01-01

    The more significant bioactivities of a variety of semicarbazones (anti-protozoa, anticonvulsant) and thiosemicarbazones (antibacterial, antifungal, antitumoral, antiviral) and their metal complexes are reviewed together with proposed mechanisms of action and structure-activity relationships. Clinical or potential pharmacological applications of these versatile compounds are discussed. PMID:14754441

  19. Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies.

    PubMed

    Karthikeyan, Subramani; Bharanidharan, Ganesan; Kesherwani, Manish; Mani, Karthik Ananth; Srinivasan, Narasimhan; Velmurugan, Devadasan; Aruna, Prakasarao; Ganesan, Singaravelu

    2016-06-01

    4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster's theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction. PMID:26368536

  20. [Differentiation activity of pyridoxal thiosemicarbazone and its copper and cobalt complexes on Friend erythroleukemia cells].

    PubMed

    Albertini, R; Gasparri Fava, G; Pinelli, S; Tarasconi, P; Starcich, B

    1991-07-01

    Thiosemicarbazones are a wide group of organic derivatives whose biological activities are a function of the parent aldehyde or ketone and of the coordination metal type. Some thiosemicarbazones possess a broad spectrum of potentially useful chemotherapeutic properties (antitumor, antibacterial, antiviral, antimalarial). The present study reports the biological effects of pyridoxal thiosemicarbazone, H2L, and relative complexes with copper, [(Cu(HL)(OH2))2]++ and with cobalt, [Co(III)(L)(HL)] on the differentiation of Friend erythroleukemia cells (FLC). They are murine proerythroblasts chronically infected by a producing Friend leukemia virus complex; their exposure to dimethylsulfoxide (Me2SO) or other chemical agents induces these cells to terminal erythroid differentiation, therefore these cells represent a good model of differentiation in vitro. Here we describe induction differentiation experiment of pyridoxal thiosemicarbazone and relative complexes of copper and cobalt on FLC performed with concentrations of 50 ug/ml (ligand), 2 ug/ml (complexes). These have little effects on cell proliferation at doses used in these experiments. Higher doses have evident cytotoxic effects. The treatment with the copper complex induces a moderate differentiation of FLC and enhances effects on erythroid differentiation of Me2SO-induced FLC. On the contrary H2L and [Co(III)(L)(HL)] haven't inducing effects or enhancing effects on Me2SO-induced FLC hemopoietic differentiation. In conclusion, the present study shows that copper complexes of pyridoxal thiosemicarbazone exert action of inducing agent and are able to enhance Me2SO-induced FLC hemopoietic differentiation. PMID:1818592

  1. Thiosemicarbazone modification of 3-acetyl coumarin inhibits Aβ peptide aggregation and protect against Aβ-induced cytotoxicity.

    PubMed

    Ranade, Dnyanesh S; Bapat, Archika M; Ramteke, Shefali N; Joshi, Bimba N; Roussel, Pascal; Tomas, Alain; Deschamps, Patrick; Kulkarni, Prasad P

    2016-10-01

    Aggregation of amyloid β peptide (Aβ) is an important event in the progression of Alzheimer's disease. Therefore, among the available therapeutic approaches to fight with disease, inhibition of Aβ aggregation is widely studied and one of the promising approach for the development of treatments for Alzheimer's disease. Thiosemicarbazone compounds are known for their variety of biological activities. However, the potential of thiosemicarbazone compounds towards inhibition of Aβ peptide aggregation and the subsequent toxicity is little explored. Herein, we report synthesis and x-ray crystal structure of novel compound 3-acetyl coumarin thiosemicarbazone and its efficacy toward inhibition of Aβ(1-42) peptide aggregation. Our results indicate that 3-acetyl coumarin thiosemicarbazone inhibits Aβ(1-42) peptide aggregation up to 80% compared to the parent 3-acetyl coumarin which inhibits 52%. Further, 3-acetyl coumarin thiosemicarbazone provides neuroprotection against Aβ-induced cytotoxicity in SH-SY5Y cell line. These findings indicate that thiosemicarbazone modification renders 3-acetyl coumarin neuroprotective properties. PMID:26232353

  2. The interplay of solvation, molecular conformation and supramolecular assembly in 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) and its N,N-dimethylformamide disolvate.

    PubMed

    Mohamed, Shaaban K; Younes, Sabry H H; Abdel-Raheem, Eman M M; Mague, Joel T; Akkurt, Mehmet; Glidewell, Christopher

    2015-11-01

    The wide diversity of applications of thiosemicarbazones and bis(thiosemicarbazones) has seen them used as anticancer and antitubercular agents, and as ligands in metal complexes designed to act as site-specific radiopharmaceuticals. Molecules of 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) {alternative name: 2,2'-[ethane-1,2-diylbis(oxy)]dibenzaldehyde bis(thiosemicarbazide)}, C18H20N6O2S2, (I), lie across twofold rotation axes in the space group C2/c, with an O-C-C-O torsion angle of -59.62 (13)° and a trans-planar arrangement of the thiosemicarbazide fragments relative to the adjacent aryl rings. The molecules of (I) are linked by N-H...S hydrogen bonds to form sheets containing R(2)4(38) rings and two types of R(2)2(8) ring. In the N,N-dimethylformamide disolvate, C18H20N6O2S2·2C3H7NO, (II), the independent molecular components all lie in general positions, but one of the solvent molecules is disordered over two sets of atomic sites having occupancies of 0.839 (3) and 0.161 (3). The O-C-C-O torsion angle in the ArOCH2CH2OAr component is -75.91 (14)° and the independent thiosemicarbazide fragments both adopt a cis-planar arrangement relative to the adjacent aryl rings. The ArOCH2CH2OAr components in (II) are linked by N-H...S hydrogen bonds to form deeply puckered sheets containing R(2)2(8), R(2)4(8) and two types of R(2)2(38) rings, and which contain cavities which accommodate all of the solvent molecules in the interior of the sheets. Comparisons are made with some related compounds. PMID:26524167

  3. The complexation of a novel squaric bis(thiosemicarbazone); 3,4-bis{[(aminothioxomethyl)amino]azamethylene}cyclobut-ene-1,2-diol

    NASA Astrophysics Data System (ADS)

    Seleem, H. S.; Ramadan, A. A. T.; Taha, A.; Eid, M. F.; Samy, F.

    2011-03-01

    A novel chelating agent (Sqtsc; H 4L) bearing both hard and soft donor atoms was synthesized by the condensation of squaric acid with thiosemicarbazide. The ligand has two symmetrical sets of donor atoms (SNO), therefore, it was allowed to react with the metal ions at the mole ratio 2:1 (M:L). Mono- and bi-nuclear chelates were obtained in which the ligand showed a variety of modes of bonding viz. (OO) 2-, (SNNS) 2- and (SNO) 2- per each metal ion supporting the ambidentate and flexidentate characters of the ligand. The mode of bonding and basicity of the ligand depend mainly on the type of the metal cation and its counter anion. All the obtained complexes have the preferable O h-geometry except the VO II-complex ( 7) which has also the preferable square pyramid geometry. Structural elucidation was achieved via elemental and spectral data.

  4. The complexation of a novel squaric bis(thiosemicarbazone); 3,4-bis{[(aminothioxomethyl)amino]azamethylene}cyclobut-ene-1,2-diol.

    PubMed

    Seleem, H S; Ramadan, A A T; Taha, A; Eid, M F; Samy, F

    2011-03-01

    A novel chelating agent (Sqtsc; H(4)L) bearing both hard and soft donor atoms was synthesized by the condensation of squaric acid with thiosemicarbazide. The ligand has two symmetrical sets of donor atoms (SNO), therefore, it was allowed to react with the metal ions at the mole ratio 2:1 (M:L). Mono- and bi-nuclear chelates were obtained in which the ligand showed a variety of modes of bonding viz. (OO)(2-), (SNNS)(2-) and (SNO)(2-) per each metal ion supporting the ambidentate and flexidentate characters of the ligand. The mode of bonding and basicity of the ligand depend mainly on the type of the metal cation and its counter anion. All the obtained complexes have the preferable O(h)-geometry except the VO(II)-complex (7) which has also the preferable square pyramid geometry. Structural elucidation was achieved via elemental and spectral data. PMID:21239220

  5. Synthesis and Structure-Activity Correlation Studies of Metal Complexes of α-N-heterocyclic Carboxaldehyde Thiosemicarbazones in Shewanella oneidensis

    PubMed Central

    Wilson, Barbara A.; Venkatraman, Ramaiyer; Whitaker, Cedrick; Tillison, Quintell

    2005-01-01

    This investigation involved the synthesis of metal complexes to test the hypothesis that structural changes and metal coordination in pyridine thiosemicarbazones affect cell growth and cell proliferation in vitro. Thiosemicarbazones are well known to possess antitumor, antiviral, antibacterial, antimalarial, and other activities. Extensive research has been carried out on aliphatic, aromatic, heterocyclic and other types of thiosemicarbazones and their metal complexes. Due to the pronounced reactivity exhibited by metal complexes of heterocyclic thiosemicarbazones, synthesis and structural characterization of di-2-pyridylketone 4N-phenyl thiosemicarbazone and diphenyl tin (Sn) and platinum (Pt) complexes were undertaken. Shewanella oneidensis MR-1, a metal ion-reducing bacterium, was used as a model organism to explore the biological activity under aerobic conditions. A comparision of the cytotoxic potential of selected ligand and metal-complex thiosemicarbazones on cell growth in wild type MR-1 and mutant DSP-010 Shewanella oneidensis strains at various concentrations (0, 5, 10, 15, 20 or 25 ppm) was performed. The wild type (MR-1) grown in the presence of increasing concentrations of Sn- thiosemicarbazone complexes was comparatively more sensitive (mean cell number = 4.8 × 108 ± 4.3 × 107 SD) than the DSP-010, a spontaneous rifampicillin derivative of the parent strain (mean cell number = 5.6 × 108 ± 6.4 × 107 SD) under comparable aerobic conditions (p=0.0004). No differences were observed in the sensitivity of the wild and mutant types when exposed to various concentrations of diphenyl Pt- thiosemicarbazone complex (p= 0.425) or the thiosemicarbazone ligand (p=0.313). Growth of MR-1 in the presence of diphenyl Sn- thiosemicarbazone was significantly different among treatment groups (p=0.012). MR-1 cell numbers were significantly higher at 5ppm than at 10 to 20ppm (p = 0.05). The mean number of DSP-010 variant strain cells also differed among diphenyl Sn

  6. Synthesis and structure-activity correlation studies of metal complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones in Shewanella oneidensis.

    PubMed

    Wilson, Barbara A; Venkatraman, Ramaiyer; Whitaker, Cedrick; Tillison, Quintell

    2005-04-01

    This investigation involved the synthesis of metal complexes to test the hypothesis that structural changesand metal coordination in pyridine thiosemicarbazones affect cell growth and cell proliferation in vitro. Thiosemicarbazones are well known to possess antitumor, antiviral, antibacterial, antimalarial, and other activities. Extensive research has been carried out on aliphatic, aromatic, heterocyclic and other types of thiosemicarbazones and their metal complexes. Due to the pronounced reactivity exhibited by metal complexes of heterocyclic thiosemicarbazones, synthesis and structural characterization of di-2-pyridylketone 4N-phenyl thiosemicarbazone and diphenyl tin (Sn) and platinum (Pt) complexes were undertaken. Shewanella oneidensis MR-1, a metal ion-reducing bacterium, was used as a model organism to explore the biological activity under aerobic conditions. A comparision of the cytotoxic potential of selected ligand and metal-complex thiosemicarbazones on cell growth in wild type MR-1 and mutant DSP-010 Shewanella oneidensis strains at various concentrations (0, 5, 10, 15, 20 or 25 ppm) was performed. The wild type (MR-1) grown in the presence of increasing concentrations of Sn- thiosemicarbazone complexes was comparatively more sensitive (mean cell number = 4.8 X 10(8) +/- 4.3 X 10(7) SD) than the DSP-010, a spontaneous rifampicillin derivative of the parent strain (mean cell number = 5.6 x 10(8) +/- 6.4 X 10(7) SD) under comparable aerobic conditions (p = 0.0004). No differences were observed in the sensitivity of the wild and mutant types when exposed to various concentrations of diphenyl Pt- thiosemicarbazone complex (p = 0.425) or the thiosemicarbazone ligand (p = 0.313). Growth of MR-1 in the presence of diphenyl Sn-thiosemicarbazone was significantly different among treatment groups (p = 0.012). MR-1 cell numbers were significantly higher at 5ppm than at 10 to 20ppm (p = 0.05). The mean number of DSP-010 variant strain cells also differed among

  7. Spectroscopic and biological studies on newly synthesized nickel(II) complexes of semicarbazones and thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Gupta, Lokesh Kumar

    2005-12-01

    Nickel(II) complexes, having the general composition Ni(L) 2X 2, have been synthesized [where L: isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC) and 4-aminoacetophenone thiosemicarbazone (LLD) and X = Cl -, 1/2SO 42-]. All the Ni(II) complexes reported here have been characterized by elemental analyses, magnetic moments, IR, electronic and mass spectral studies. All the complexes were found to have magnetic moments corresponding to two unpaired electrons. The possible geometries of the complexes were assigned on the basis of electronic and infrared spectral studies. Newly synthesized ligand and its nickel(II) complexes have been screened against different bacterial and fungal growth.

  8. Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

    PubMed

    Taşdemir, Demet; Karaküçük-İyidoğan, Ayşegül; Ulaşli, Mustafa; Taşkin-Tok, Tuğba; Oruç-Emre, Emİne Elçİn; Bayram, Hasan

    2015-02-01

    A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. PMID:25399965

  9. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes.

    PubMed

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  10. Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex.

    PubMed

    Vutey, Venn; Castelli, Silvia; D'Annessa, Ilda; Sâmia, Luciana B P; Souza-Fagundes, Elaine M; Beraldo, Heloisa; Desideri, Alessandro

    2016-09-15

    The human topoisomerase IB inhibition and the antiproliferative activity of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone HPyCT4BrPh alone and its copper(II) complex [Cu(PyCT4BrPh)Cl] was investigated. [Cu(PyCT4BrPh)Cl] inhibits both the DNA cleavage and religation step of the enzyme, whilst the ligand alone does not display any effect. In addition we show that coordination to copper(II) improves the cytotoxicity of HPyCT4BrPh against THP-1 leukemia and MCF-7 breast cancer cells. The data indicate that the copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds. PMID:27431056

  11. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes

    PubMed Central

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  12. Monitoring cellular uptake and cytotoxicity of copper(II) complex using a fluorescent anthracene thiosemicarbazone ligand.

    PubMed

    Kate, Anup N; Kumbhar, Anupa A; Khan, Ayesha A; Joshi, Pranaya V; Puranik, Vedavati G

    2014-01-15

    The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase. PMID:24328322

  13. Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates.

    PubMed

    Blau, Lorena; Menegon, Renato Farina; Trossini, Gustavo H G; Molino, João Vitor Dutra; Vital, Drielli Gomes; Cicarelli, Regina Maria Barretto; Passerini, Gabriela Duó; Bosquesi, Priscila Longhin; Chin, Chung Man

    2013-09-01

    The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Trypanosoma cruzi in in vitro assays (IC50 < 57 μM), and no mutagenic profile was observed in micronucleous tests. Although the in vitro inhibition test showed that 10-μM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity. PMID:23851115

  14. Spectroscopic, thermal and electrochemical studies on some nickel(II) thiosemicarbazone complexes

    NASA Astrophysics Data System (ADS)

    El-Shazly, R. M.; Al-Hazmi, G. A. A.; Ghazy, S. E.; El-Shahawi, M. S.; El-Asmy, A. A.

    2005-01-01

    Several complexes of thiosemicarbazone derivatives with Ni(II) have been prepared. Structural investigation of the ligands and their complexes has been made based on elemental analysis, magnetic moment, spectral (UV-Vis, i.r., 1H NMR, ms), and thermal studies. The i.r. spectra suggest the bidentate mononegative and tridentate (neutral, mono-, and binegative) behavior of the ligands. Different stereochemistries were suggested for the isolated complexes. The thermogravimetry (TG) and derivative thermogravimetry (DTG) have been used to study the thermal decomposition and kinetic parameters of some ligands and complexes using the Coats-Redfern and Horowitz-Metzger equations. The redox properties and stability of the complexes toward oxidation waves explored by cyclic voltammetry are related to the electron withdrawing or releasing ability of the substituent of thiosemicarbazone moiety. The samples displayed Ni II/Ni I couples irreversible waves associated with Ni III/Ni II process.

  15. Structural studies on acetophenone- and benzophenone-derived thiosemicarbazones and their zinc(II) complexes

    NASA Astrophysics Data System (ADS)

    Ferraz, Karina S. O.; Silva, Nayane F.; Da Silva, Jeferson G.; Speziali, Nivaldo L.; Mendes, Isolda C.; Beraldo, Heloisa

    2012-01-01

    In the present work N(3)- meta-chlorophenyl-(HAc3 mCl, 1) and N(3)- meta-fluorphenyl-(HAc3 mF, 2) acetophenone thiosemicarbazone, and N(3)- meta-chlorophenyl-(HBz3 mCl, 3) and N(3)- meta-fluorphenyl-(HBz3 mF, 4) benzophenone thiosemicarbazone were obtained, as well as their zinc(II) complexes [Zn(Ac3 mCl) 2] ( 5), [Zn(Ac3 mF) 2] ( 6), [Zn(Bz3 mCl) 2] ( 7) and [Zn(Bz3 mF) 2] ( 8). Upon re-crystallization in DMSO:acetone conversion of 8 into [Zn(Bz3 mF) 2]·(DMSO) ( 8a) occurred. The crystal structures of 2, 5 and 8a were determined.

  16. Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors.

    PubMed

    Hameed, Abdul; Khan, Khalid Mohammed; Zehra, Syeda Tazeen; Ahmed, Ramasa; Shafiq, Zahid; Bakht, Syeda Mahwish; Yaqub, Muhammad; Hussain, Mazhar; de la Vega de León, Antonio; Furtmann, Norbert; Bajorath, Jürgen; Shad, Hazoor Ahmad; Tahir, Muhammad Nawaz; Iqbal, Jamshed

    2015-08-01

    Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 μM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 μM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones. PMID:26119990

  17. Syntheses, structural and spectral studies of six-coordinate, [Ph 2SnCl(acpm)], and seven-coordinate, [ nBu 2Sn(dapm)], diorganotin(IV) complexes with N, N, S-tridentate and S, N, N, N, S-pentadentate N4-heterocyclic thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    de Sousa, Gerimário F.; Manso, Luís Carlos C.; Lang, Ernesto S.; Gatto, Claudia C.; Mahieu, Bernard

    2007-01-01

    The reaction of the N, N, S-tridentate ligand 2-acetylpyridine ( N4-morpholyl thiosemicarbazones), Hacpm, with Ph 2SnCl 2 leads to the formation of the six-coordinate complex [Ph 2SnCl(acpm)] ( 1), whereas the reaction of the S, N, N, N, S-pentadentate ligand 2,6-diacetylpyridine bis( N4-morpholyl thiosemicarbazone), H 2dapm, with nBu 2SnCl 2 leads to the formation of the seven-coordinate complex [ nBu 2Sn(dapm)] ( 2). Both compounds were studied by microanalyses, IR, NMR ( 1H, 13C, 119Sn) and Mössbauer spectroscopy to investigate their structural properties. The organotin(IV) complexes were also studied by single crystal X-ray diffraction and the structure determination revealed that the phenyl derivative crystallizes in the triclinic space group (P1¯) as discrete neutral molecules, with the tin(IV) ion in a distorted octahedral geometry with the acpm 1- ligand in a meridional configuration and the phenyl groups in trans positions. X-ray analysis shows that the n-butyl complex crystallizes in the monoclinic space group ( P2 1/ c) as discrete neutral complexes, with the tin(IV) ion in a distorted pentagonal bipyramidal geometry. A correlation between Mössbauer and X-ray data based on the point-charge model is discussed.

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

    PubMed

    Lovejoy, David B; Richardson, Des R

    2002-07-15

    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. PMID:12091363

  19. 1-Methylisatin 3-Thiosemicarbazone Treatment of NZB × NZW Hybrid Mice

    PubMed Central

    Gabriel, R.

    1971-01-01

    Female B/W mice have been treated with the anti-viral agent 1-Methylisatin 3-Thiosemicarbazone. The drug was given upon the day of birth and weekly until death. There was a delay in the development of proteinuria and positive antinuclear factor. The mean survival of the group was prolonged; eventually all mice died from nephritis within a 6 week period. The results are interpreted as a suppression of viral activity in these animals. PMID:5314564

  20. Spectroscopic characterization of copper(II) complexes of indoxyl N(4)-methyl thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Kumar, Umendra

    2004-10-01

    New copper(II) complexes of indoxyl thiosemicarbazone (ITSC) of general composition CuL 2X 2 (where L: ITSC; X: Cl -, NO 3-, ClO 4-, NCS -) have been synthesized and characterized by elemental analysis, molar conductance, magnetic susceptibility measurements and spectral (electronic, IR, EPR, 1H NMR , Mass) studies. Cyclic voltammetry measurements show quasi-reversible Cu 2+/Cu 1+ couple. Various physico-chemical techniques suggest a tetragonal structure for these copper(II) complexes.

  1. Bivalent transition metal complexes of coumarin-3-yl thiosemicarbazone derivatives: Spectroscopic, antibacterial activity and thermogravimetric studies

    NASA Astrophysics Data System (ADS)

    Refat, Moamen S.; El-Deen, Ibrahim M.; Anwer, Zeinab M.; El-Ghol, Samir

    2009-02-01

    Schiff base complexes of Cu(II), Co(II) and Ni(II) with two coumarin-3-yl thiosemicarbazone derivatives (1E)-1-(1-(2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (OCET) and (1E)-1-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (BOCET) were synthesized by the reaction of Cu(II), Co(II) and Ni(II) chlorides with each mentioned ligand with molar ratio 1:2 metal-to-ligand. Both ligands and their metal complexes were characterized by different physicochemical methods, elemental analysis, molar conductivity, (UV-vis, Mass, Infrared, 1H NMR spectra) and also thermal analysis (TG and DTG) techniques. The discussion of the outcome data of the prepared complexes indicate that the coumarin-3-yl thiosemicarbazone derivatives ligands behave as a bidentate ligand through both thione sulphur and azomethine nitrogen with 1:2 (metal:ligand) stoichiometry for all complexes. The molar conductance measurements proved that the complexes are electrolytes. The kinetic thermodynamic parameters such as: E∗, Δ H∗, Δ S∗and Δ G∗are calculated from the DTG curves, all complexes are more ordered except Ni(II) complexes. The antibacterial activity of the coumarin-3-yl thiosemicarbazone derivatives and their metal complexes was evaluated against some kinds of Gram positive and Gram negative bacteria.

  2. Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease.

    PubMed

    Rogolino, Dominga; Bacchi, Alessia; De Luca, Laura; Rispoli, Gabriele; Sechi, Mario; Stevaert, Annelies; Naesens, Lieve; Carcelli, Mauro

    2015-10-01

    The influenza virus PA endonuclease is an attractive target for the development of novel anti-influenza virus therapeutics, which are urgently needed because of the emergence of drug-resistant viral strains. Reported PA inhibitors are assumed to chelate the divalent metal ion(s) (Mg²⁺ or Mn²⁺) in the enzyme's catalytic site, which is located in the N-terminal part of PA (PA-Nter). In the present work, a series of salicylaldehyde thiosemicarbazone derivatives have been synthesized and evaluated for their ability to inhibit the PA-Nter catalytic activity. Compounds 1-6 have been evaluated against influenza virus, both in enzymatic assays with influenza virus PA-Nter and in virus yield assays in MDCK cells. In order to establish a structure-activity relationship, the hydrazone analogue of the most active thiosemicarbazone has also been evaluated. Since chelation may represent a mode of action of such class of molecules, we studied the interaction of two of them, one with and one without biological activity versus the PA enzyme, towards Mg²⁺, the ion that is probably involved in the endonuclease activity of the heterotrimeric influenza polymerase complex. The crystal structure of the magnesium complex of the o-vanillin thiosemicarbazone ligand 1 is also described. Moreover, docking studies of PA endonuclease with compounds 1 and 2 were performed, to further analyse the possible mechanism of action of this class of inhibitors. PMID:26323352

  3. Microwave synthesis of mixed ligand diimine–thiosemicarbazone complexes of ruthenium(ii): biophysical reactivity and cytotoxicity†

    PubMed Central

    Beckford, Floyd A.; Shaloski, Michael; Leblanc, Gabriel; Thessing, Jeffrey; Lewis-Alleyne, Lesley C.; Holder, Alvin A.; Li, Liya; Seeram, Navindra P.

    2010-01-01

    A novel microwave-assisted synthetic method has been used to synthesise a series of mixed ligand ruthenium(ii) compounds containing diimine as well as bidentate thiosemicarbazone ligands. The compounds contain the diimine 1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy) and the thiosemicarbazone is derived from 9-anthraldehyde. Based on elemental analyses and spectroscopic data, the compounds are best formulated as [(phen)2Ru(thiosemicarbazone)](PF6)2 and [(phen)2Ru(thiosemicarbazone)](PF6)2 where thiosemicarbazone = 9-anthraldehydethiosemicarbazone, 9-anthraldehyde-N(4)-methylthiosemicarbazone, and 9-anthraldehyde-N(4)-ethylthiosemicarbazone. Fluorescence competition studies with ethidium bromide, along with viscometric measurements suggests that the complexes bind calf thymus DNA (CTDNA) relatively strongly via an intercalative mode possibly involving the aromatic rings of the diimine ligands. The complexes show good cytotoxic profiles against MCF-7 and MDA-MB-231 (breast adenocarcinoma) as well as HCT 116 and HT-29 (colorectal carcinoma) cell lines. PMID:20023905

  4. Zinc(II)-Thiosemicarbazone Complexes Are Localized to the Lysosomal Compartment Where They Transmetallate with Copper Ions to Induce Cytotoxicity.

    PubMed

    Stacy, Alexandra E; Palanimuthu, Duraippandi; Bernhardt, Paul V; Kalinowski, Danuta S; Jansson, Patric J; Richardson, Des R

    2016-05-26

    As the di-2-pyridylketone thiosemicarbazone (DpT) and 2-acetylpyridine thiosemicarbazone (ApT) series show potent antitumor activity in vitro and in vivo, we synthesized their fluorescent zinc(II) complexes to assess their intracellular distribution. The Zn(II) complexes generally showed significantly greater cytotoxicity than the thiosemicarbazones alone in several tumor cell-types. Notably, specific structure-activity relationships demonstrated the importance of the di-2-pyridyl pharmacophore in their activity. Confocal fluorescence imaging and live cell microscopy showed that the Zn(II) complex of our lead compound, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), which is scheduled to enter clinical trials, was localized to lysosomes. Under lysosomal conditions, the Zn(II) complexes were shown to transmetallate with copper ions, leading to redox-active copper complexes that induced lysosomal membrane permeabilization (LMP) and cytotoxicity. This is the first study to demonstrate direct lysosomal targeting of our novel Zn(II)-thiosemicarbazone complexes that mediate their activity via transmetalation with copper ions and LMP. PMID:27023111

  5. Bis(chloromethyl)ether (BCME)

    Integrated Risk Information System (IRIS)

    Bis ( chloromethyl ) ether ( BCME ) ; CASRN 542 - 88 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments f

  6. Bis(chloroethyl)ether (BCEE)

    Integrated Risk Information System (IRIS)

    Bis ( chloroethyl ) ether ( BCEE ) ; CASRN 111 - 44 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments fo

  7. Bis(2-chloroethoxy)methane

    Integrated Risk Information System (IRIS)

    Bis ( 2 - chloroethoxy ) methane ; CASRN 111 - 91 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  8. Synthesis, characterization and binding affinities of rhenium(I) thiosemicarbazone complexes for the estrogen receptor (α/β).

    PubMed

    Núñez-Montenegro, Ara; Carballo, Rosa; Vázquez-López, Ezequiel M

    2014-11-01

    The binding affinities towards estrogen receptors (ERs) α and β of a set of thiosemicarbazone ligands (HL(n)) and their rhenium(I) carbonyl complexes [ReX(HL(n))(CO)3] (X=Cl, Br) were determined by a competitive standard radiometric assay with [(3)H]-estradiol. The ability of the coordinated thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX bond were used as a synthetic strategy to obtain [Re(hpy)(L(n))(CO)3] (hpy=3- or 4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new thiosemicarbazonate complexes with an improved affinity towards the estrogen receptors and, consequently, the values of the inhibition constant (Ki) could be determined for some of them. In general, the values of Ki for both ER subtypes suggest an appreciable selectivity towards ERα. PMID:25061691

  9. Inactivation of lambda phage infectivity and lambda deoxyribonucleic acid transfection by N-methyl-isatin beta-thiosemicarbazone-copper complexes.

    PubMed

    Levinson, W; Helling, R

    1976-01-01

    The infectivity of intact lambda phage and transfection by lambda deoxyribonucleic acid were inactivated by exposure to the copper complexes of N-methyl-isatin beta-thiosemicarbazone, thiosemicarbazide, and semicarbazide, but not methyl-isatin. No inactivation was observed when these compounds were used in the absence of copper sulfate. This confirms our previous observation that the activity of N-methyl-isatin beta-thiosemicarbazone is mediated by its thiosemicarbazone moiety and that the presence of copper is required for action. This represents the first time, to our knowledge, that semicarbazide has been found to possess antiviral activity. It is clear that these compounds act directly on deoxyribonucleic acid; whether the compounds also act on proteins has not been determined. PMID:769669

  10. On the verification of binding modes of p-dimethylaminobenzaldehyde thiosemicarbazone with mercury(II). The solid state studies

    NASA Astrophysics Data System (ADS)

    Trzesowska-Kruszynska, Agata

    2014-08-01

    Two coordination compounds of p-dimethylaminobenzaldehyde thiosemicarbazone, fluorescent chemosensor, have been synthesised from the mercury(II) nitrate and mercury(II) chloride, and subsequently characterised by IR spectroscopy, thermal analysis, as well as single crystal X-ray diffraction technique. The inorganic anion has a distinct influence on binding mode of thiosemicarbazone ligand to Hg(II) ion. In both compounds the metal to ligand stoichiometry is 1:2 and the organic ligands coordinate to Hg ion in the neutral thione form, but they differ in a ligand binding mode and the conformation of the ligand. The crystal packing of mercury(II) nitrate complex with thiosemicarbazone is controlled by the mercury chelate ring-phenylene ring π···π stacking interactions.

  11. Inhibition of respiratory complex I by copper(ii)-bis(thiosemicarbazonato) complexes.

    PubMed

    Djoko, Karrera Y; Donnelly, Paul S; McEwan, Alastair G

    2014-12-01

    Several copper(ii) complexes of bis(thiosemicarbazones) [Cu(btsc)s] show promise as therapeutics for the treatment of neurological diseases, cancers and bacterial infections. These complexes are thought to act primarily as copper ionophores or "copper boosting" agents, whereby the Cu(II) centre is reduced by cytosolic reductants and Cu(I) is released as "free" or "bioavailable" ion. It is then assumed that the dissociated Cu(I) ion is the species responsible for many of the observed biological effects of Cu(btsc)s. We recently showed that Cu(btsc) complexes inhibited NADH dehydrogenases in the bacterial respiratory chain. In this work, we demonstrate that Cu(btsc) complexes also inhibit mitochondrial respiration and that Complex I in the mitochondrial electron transport chain is a specific target of inhibition. However, bioavailable Cu ions do not appear to contribute to the action of Cu(btsc) as a respiratory inhibitor. Instead, an intact Cu(btsc) molecule may bind reversibly and competitively to the site of ubiquinone binding in Complex I. Our results add to the growing body of evidence that the intact complex may be important in the overall cellular activity of Cu(btsc) complexes and further the understanding of their biological effects as a potential therapeutic. PMID:25366244

  12. 40 CFR 721.1630 - 1,2-Ethanediol bis(4-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- -1,2-ethanediyl] bis(oxy)]bis-, bis(4-methylbenzene sulfonate); and ethanol, 2- oxy]ethoxy]...

  13. 40 CFR 721.1630 - 1,2-Ethanediol bis(4-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- -1,2-ethanediyl] bis(oxy)]bis-, bis(4-methylbenzene sulfonate); and ethanol, 2- oxy]ethoxy]...

  14. 40 CFR 721.1630 - 1,2-Ethanediol bis(4-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- -1,2-ethanediyl] bis(oxy)]bis-, bis(4-methylbenzene sulfonate); and ethanol, 2- oxy]ethoxy]...

  15. 40 CFR 721.1630 - 1,2-Ethanediol bis(4-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- -1,2-ethanediyl] bis(oxy)]bis-, bis(4-methylbenzene sulfonate); and ethanol, 2- oxy]ethoxy]...

  16. 40 CFR 721.1630 - 1,2-Ethanediol bis(4-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-methylbenzenesulfonate); 2,2-oxybis-ethane bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- bis-, bis(4-methylbenzenesulfonate); ethanol, 2,2â²- -1,2-ethanediyl] bis(oxy)]bis-, bis(4-methylbenzene sulfonate); and ethanol, 2- oxy]ethoxy]...

  17. Strong effect of copper(II) coordination on antiproliferative activity of thiosemicarbazone-piperazine and thiosemicarbazone-morpholine hybrids.

    PubMed

    Bacher, Felix; Dömötör, Orsolya; Chugunova, Anastasia; Nagy, Nóra V; Filipović, Lana; Radulović, Siniša; Enyedy, Éva A; Arion, Vladimir B

    2015-05-21

    In this study, 2-formylpyridine thiosemicarbazones and three different heterocyclic pharmacophores were combined to prepare thiosemicarbazone–piperazine mPip-FTSC (HL1) and mPip-dm-FTSC (HL2), thiosemicarbazone–morpholine Morph-FTSC (HL3) and Morph-dm-FTSC (HL4), thiosemicarbazone–methylpyrrole-2-carboxylate hybrids mPyrr-FTSC (HL5) and mPyrr-dm-FTSC (HL6) as well as their copper(II) complexes [CuCl(mPipH-FTSC-H)]Cl (1 + H)Cl, [CuCl(mPipH-dm-FTSC-H)]Cl (2 + H)Cl, [CuCl(Morph-FTSC-H)] (3), [CuCl(Morph-dm-FTSC-H)] (4), [CuCl(mPyrr-FTSC-H)(H2O)] (5) and [CuCl(mPyrr-dm-FTSC-H)(H2O)] (6). The substances were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy (HL1–HL6), ESI mass spectrometry, IR and UV–vis spectroscopy and single crystal X-ray diffraction (1–5). All compounds were prepared in an effort to generate potential antitumor agents with an improved therapeutic index. In addition, the effect of structural alterations with organic hybrids on aqueous solubility and copper(II) coordination ability was investigated. Complexation of ligands HL2 and HL4 with copper(II) was studied in aqueous solution by pH-potentiometry, UV–vis spectrophotometry and EPR spectroscopy. Proton dissociation processes of HL2 and HL4 were also characterized in detail and microscopic constants for the Z/E isomers were determined. While the hybrids HL5, HL6 and their copper(II) complexes 5 and 6 proved to be insoluble in aqueous solution, precluding antiproliferative activity studies, the thiosemicarbazone–piperazine and thiosemicarbazone–morpholine hybrids HL1–HL4, as well as copper(II) complexes 1–4 were soluble in water enabling cytotoxicity assays. Interestingly, the metal-free hybrids showed very low or even a lack of cytotoxicity (IC50 values > 300 μM) in two human cancer cell lines HeLa (cervical carcinoma) and A549 (alveolar basal adenocarcinoma), whereas their copper(II) complexes were cytotoxic showing IC50 values from 25.5 to 65.1

  18. Spectral characterization and crystal structure of tetrahydropyran-4-one thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Umamatheswari, S.; Jaya Pratha, J.; Kabilan, S.

    2011-03-01

    ( E)-1-(Tetrahydro-3-methyl-2,6-diphenylpyran-4-ylidene) thiosemicarbazide ( 3) and ( E)-1-(2,6- bis(4-chlorophenyl)-tetrahydro-3,5-dimethylpyran-4-ylidene) thiosemicarbazide ( 4) were obtained and characterized by FT-IR, 1H NMR, 13C NMR, NOESY spectroscopy and X-ray single-crystal diffraction analysis. Molecular orbital calculations have been carried out for 3 and 4 by using an ab initio method (HF) and also density functional method (B3LYP) at 6-31G basis set. Compound 4 crystallizes in the monoclinic system, space group P2 1/c, with a = 11.9645(3) Å, b = 20.0690(6) Å, c = 8.7441(2) Å, β = 105.5220(10)°, V = 2023.02(9) Å 3, and Z = 4. Compounds 3 and 4 exist in chair conformation with equatorial orientation of all the substituents at pyran ring except the methyl group at C-5 of compound 4 which is oriented at axial disposition to stabilise the chair conformation and the configuration about the C dbnd N double bond is syn to C-5 carbon ( E-form).

  19. Manganese(II) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents.

    PubMed

    Oliveira, Carolina G; da S Maia, Pedro Ivo; Souza, Paula C; Pavan, Fernando R; Leite, Clarice Q F; Viana, Rommel B; Batista, Alzir A; Nascimento, Otaciro R; Deflon, Victor M

    2014-03-01

    Through a systematic variation on the structure of a series of manganese complexes derived from 2-acetylpyridine-N(4)-R-thiosemicarbazones (Hatc-R), structural features have been investigated with the aim of obtaining complexes with potent anti-Mycobacterium tuberculosis activity. The analytical methods used for characterization included FTIR, EPR, UV-visible, elemental analysis, cyclic voltammetry, magnetic susceptibility measurement and single crystal X-ray diffractometry. Density functional theory (DFT) calculations were performed in order to evaluate the contribution of the thiosemicarbazonate ligands on the charge distribution of the complexes by changing the peripheral groups as well as to verify the Mn-donor atoms bond dissociation predisposition. The results obtained are consistent with the monoanionic N,N,S-tridentate coordination of the thiosemicarbazone ligands, resulting in octahedral complexes of the type [Mn(atc-R)2], paramagnetic in the extension of 5 unpaired electrons, whose EPR spectra are consistent for manganese(II). The electrochemical analyses show two nearly reversible processes, which are influenced by the peripheral substituent groups at the N4 position of the atc-R(1-) ligands. The minimal inhibitory concentration (MIC) of these compounds against M. tuberculosis as well as their in vitro cytotoxicity on VERO and J774A.1 cells (IC50) was determined in order to find their selectivity index (SI) (SI=IC50/MIC). The results evidenced that the compounds described here can be considered as promising anti-M. tuberculosis agents, with SI values comparable or better than some commercial drugs available for the tuberculosis treatment. PMID:24188534

  20. Microwave assisted synthesis, X-ray crystallography and DFT calculations of selected aromatic thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Serda, Maciej; Małecki, Jan G.; Mrozek-Wilczkiewicz, Anna; Musioł, Robert; Polański, Jarosław

    2013-04-01

    Series of four benzaldehyde thiosemicarbazones has been synthesized under microwave irradiation and characterized structurally by means of infrared and NMR spectroscopies and mass spectrometry. Their crystal structures were determined by single crystal X-ray analysis followed by DFT calculations. Partial charges on the molecular surface and dipole moments of the structures were calculated. Crystal structures are stabilized by intramolecular hydrogen bonding and stacking interactions. Studied compounds are interesting as antiproliferative and antifungal agents acting through interactions with iron. Thus presented results may be useful in design new more active or specific structures.

  1. Synthesis and spectroscopic study on photochromism of a new thiosemicarbazone compound containing pyrazolone

    NASA Astrophysics Data System (ADS)

    Chai, Hui; Liu, Guangfei; Liu, Lang; Jia, Dianzeng

    2005-09-01

    A new photochromic compound 1,3-diphenyl-4-(4'-fluro)benzal-5-pyrazolone-4-ethyl thiosemicarbazone (DP4FBP-ETSC) was synthesized by direct condensation of 1,3-diphenyl-5-pyrazolone with N(4)-ethyl thiosemicarbazide. The product was characterized by elemental analysis, IR and 1H NMR spectra. The photochromic properties of the compound were studied using time-dependent fluorescence emission spectra, the UV-vis reflection spectra in the solid state and the UV-vis absorption spectroscopy in liquid. The reaction rate constant of compound was also analyzed. The results show that DP4FBP-ETSC can perform photochromism.

  2. Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

    PubMed Central

    Mallari, Jeremy P.; Shelat, Anang; Kosinski, Aaron; Caffrey, Conor R.; Connelly, Michele; Zhu, Fangyi; McKerrow, James H.; Guy, R. Kiplin

    2008-01-01

    Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T.brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T.brucei, and specificity was assessed with a panel of four mammalian cell lines. PMID:18420405

  3. Spectral studies of coordination compounds of cobalt(II) with thiosemicarbazone of heterocyclic ketone

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Kumar, Umendra

    2005-12-01

    The paper presents the spectral analysis of cobalt(II) complexes with indoxyl thiosemicarbazone (ITSC) of general composition [CoL 2X 2] (where L = ITSC, X = Cl -, NO 3-, (1/2)SO 42-, NCS -). The geometry of the complexes have been characterized by elemental analysis, molar conductance, magnetic susceptibility measurements and spectral (electronic, IR, EPR, 1H NMR, mass) studies. The various physico-chemical techniques suggested a coordination number of six (octahedral) for chloro, nitrato and thiocyanato complexes. Whereas sulfato complex was found to have five coordinate trigonal-bipyramidal geometry. All the complexes are of high spin type showing magnetic moment corresponding to three unpaired electrons.

  4. The supramolecular chemistry of thiosemicarbazones derived from pyrrole: a structural view

    NASA Astrophysics Data System (ADS)

    Alonso, Ruben; Bermejo, Elena; Carballo, Rosa; Castiñeiras, Alfonso; Pérez, Teresa

    2002-03-01

    Condensation of 2-formylpyrrole or 2-acetylpyrrole with thiosemicarbazide or with N-methyl-, N-ethyl-, N-phenyl- or (for 2-formylpyrrole) N-dimethylthiosemicarbazide afforded nine thiosemicarbazones that were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopy and, when possible, X-ray-diffractometric structure analysis. N-H⋯S hydrogen bonds (and N-H⋯O and/or O-H⋯S bonds in the structures with water or DMSO of crystallization) give rise to supramolecular structures that in some cases are probably stabilized by π-π interactions.

  5. Coordination Chemistry of Polyaromatic Thiosemicarbazones 2: Synthesis and Biological Activity of Zinc, Cobalt, and Copper Complexes of 1-(Naphthalene-2-yl)ethanone Thiosemicarbazone

    PubMed Central

    LeBlanc, Marc-Andre; Gonzalez-Sarrías, Antonio; Beckford, Floyd A.; Mbarushimana, P. Canisius; Seeram, Navindra P.

    2012-01-01

    A novel thiosemicarbazone from 2-acetonaphthone (represented as acnTSC) has been synthesized and its basic coordination chemistry with zinc(II), cobalt(II), and copper(II) explored. The complexes were characterized by elemental analysis and various spectroscopic techniques and are best formulated as [M(acnTSC)2Cl2] with the metal likely in an octahedral environment. The anticancer activity of the complexes was determined against a panel of human colon cancer cells (HCT-116 and Caco-2). The compounds bind to DNA via an intercalative mode with binding constants of 9.7 × 104 M−1, 1.8 × 105 M−1, and 9.5 × 104 M−1 for the zinc, cobalt, and copper complexes, respectively. PMID:22303515

  6. Synthesis, experimental and theoretical studies on its crystal structure and FT-IR spectrum of new thiosemicarbazone compound E-2-(4-isopropylbenzylidene)thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Khalaji, Aliakbar Dehno; Mehrani, Sepideh; Eigner, Vaclav; Dusek, Michal

    2013-09-01

    The title compound E-2-(4-isopropylbenzylidene)thiosemicarbazone (1) derived from the reaction of 4-isopropylbenzaldehyde and thiosemicarbazide in ethanol solution has been synthesized and characterized by elemental analyses, FT-IR and 1H NMR spectroscopy and single-crystal X-ray diffraction. Its optimized geometry together with the theoretical assignment of the vibrational frequencies of the title compound has been computed by using density functional theory (DFT) method. In the gas phase the four conformers of the title compound were found and it was found that the conformer Sn1 is the most stable one. The title compound crystallizes in the monoclinic space group P21/c with unit cell parameters: a = 14.4054(4), b = 5.6832(10), c = 14.4337(3) Å, β = 93.306(2)°, V = 1179.70(5) Å3 and Z = 4.

  7. Syntheses and spectroscopic studies on zinc(II) and mercury(II) complexes of isatin-3-thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Akinchan, N. T.; Drożdżewski, P. M.; Holzer, W.

    2002-10-01

    Zinc(II) and mercury(II) complexes were prepared by reacting isatin-3-thiosemicarbazone (ISTSCH) with zinc(II) acetate or mercury(II) bromide. The complexes were characterized by IR, Raman, diffuse reflectance, 1H and 13C NMR spectra and elemental analysis. Tetrahedral structures for Zn(ISTSC) 2 and Hg(ISTSCH)Br 2 are suggested.

  8. Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.

    PubMed

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2016-06-01

    The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts. PMID:26951232

  9. Examination of the Impact of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIα.

    PubMed

    Wilson, James T; Jiang, Xiaohua; McGill, Bradley C; Lisic, Edward C; Deweese, Joseph E

    2016-04-18

    Type II DNA topoisomerases resolve topological knots and tangles in DNA that result from routine cellular processes and are effective targets for anticancer therapeutics. To this end, thiosemicarbazones have been identified as having the ability to kill cancer cells from several cell lines. Literature evidence suggests that at least some thiosemicarbazones have an impact on topoisomerase II activity. However, the mechanism is not as clearly defined. Therefore, we set out to analyze the activity of four α-(N)-heterocyclic thiosemicarbazone compounds against topoisomerase IIα. The ligands, acetylpyridine-ethylthiosemicarbazone (APY-ETSC) and acetylpyrazine-methylthiosemicarbazone (APZ-MTSC), and their copper(II) [Cu(II)] complexes [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] were examined for the ability to impact the catalytic cycle of human topoisomerase IIα. Both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] were more effective at inhibiting DNA relaxation compared with the ligands alone. Further, both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] increased double-stranded DNA cleavage levels without inhibiting topoisomerase IIα-mediated DNA ligation. The Cu(II) complexes inactivate enzyme activity over time suggesting a critical interaction with the enzyme. Additionally, we found that the Cu(II)-thiosemicarbazone complexes do not significantly impact DNA cleavage by the catalytic core of the enzyme. This evidence is supported by the fact that both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl], and to a lesser extent the ligands, inhibit topoisomerase IIα-mediated ATP hydrolysis. Based upon kinetic analysis, the Cu(II) complexes appear to be noncompetitive inhibitors of the ATPase domain of topoisomerase IIα. Taken together, our results provide evidence that Cu(II) complexes of α-(N)-heterocyclic thiosemicarbazones catalytically inhibit the enzyme through the ATPase domain but also promote double-stranded DNA cleavage by the enzyme. PMID:26982206

  10. BIS Handbook: An Organizational Manual & Directory. Revised.

    ERIC Educational Resources Information Center

    Association of Coll. and Research Libraries, Chicago, IL. Bibliographic Instruction Section.

    This handbook was prepared for the officers and committee members of the ACRL (Association of College and Research Libraries) Bibliographic Instruction Section (BIS). Published annually, the handbook details the organizational structure of BIS, provides procedural information, and highlights section activities and resources. In addition, the…

  11. Spectral characterization of iron(III) complexes of 2-benzoylpyridine N(4)-substituted thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Joseph, Marthakutty; Sreekanth, Anandaram; Suni, V.; Kurup, M. R. Prathapachandra

    2006-06-01

    Three iron(III) complexes (1-3) of 2-benzoylpyridine N(4)-phenyl thiosemicarbazone (HL 1) and one iron(III) complex (4) of 2-benzoylpyridine N(4)-cyclohexyl thiosemicarbazone (HL 2) were synthesized and characterized by means of different physicochemical techniques viz., molar conductivity measurements, magnetic susceptibility studies and electronic, infrared and EPR spectral studies. The analytical data and the molar conductance measurements of the complexes reveal that two molecules of the ligand and the anion are coordinated to the metal atom in all the four complexes. The magnetic moments of the complexes suggest that they are of low spin. From the infrared spectra of the ligands and the complexes it is confirmed that the ligands coordinate to iron(III) as an anion coordinating via the azomethine nitrogen, pyridyl nitrogen, and the thiolate sulphur. The EPR spectra of the complexes in the polycrystalline state at 298 and 110 K and in DMF solution at 110 K were recorded and all the spectra show three g values indicating that these complexes have rhombic distortion. All the iron(III) complexes in DMF solution at 110 K have similar anisotropic spectra with almost the same gav values, indicating that the bonding in all the complexes is similar and is unaffected by the coordination of the anion.

  12. Mononuclear ruthenium(III) complexes containing chelating thiosemicarbazones: Synthesis, characterization and catalytic property

    NASA Astrophysics Data System (ADS)

    Raja, N.; Ramesh, R.

    2010-02-01

    Mononuclear ruthenium(III) complexes of the type [RuX(EPh 3) 2(L)] (E = P or As; X = Cl or Br; L = dibasic terdentate dehydroacetic acid thiosemicarbazones) have been synthesized from the reaction of thiosemicarbazone ligands with ruthenium(III) precursors, [RuX 3(EPh 3) 3] (where E = P, X = Cl; E = As, X = Cl or Br) and [RuBr 3(PPh 3) 2(CH 3OH)] in benzene. The compositions of the complexes have been established by elemental analysis, magnetic susceptibility measurement, FT-IR, UV-vis and EPR spectral data. These complexes are paramagnetic and show intense d-d and charge transfer transitions in dichloromethane. The complexes show rhombic EPR spectra at LNT which are typical of low-spin distorted octahedral ruthenium(III) species. All the complexes are redox active and display an irreversible metal centered redox processes. Complex [RuCl(PPh 3) 2(DHA-PTSC)] ( 5) was used as catalyst for transfer hydrogenation of ketones in the presence of isopropanol/KOH and was found to be the active species.

  13. Vanadium(IV/V) complexes of Triapine and related thiosemicarbazones: Synthesis, solution equilibrium and bioactivity.

    PubMed

    Kowol, Christian R; Nagy, Nóra V; Jakusch, Tamás; Roller, Alexander; Heffeter, Petra; Keppler, Bernhard K; Enyedy, Éva A

    2015-11-01

    The stoichiometry and thermodynamic stability of vanadium(IV/V) complexes of Triapine and two related α(N)-heterocyclic thiosemicarbazones (TSCs) with potential antitumor activity have been determined by pH-potentiometry, EPR and (51)V NMR spectroscopy in 30% (w/w) dimethyl sulfoxide/water solvent mixtures. In all cases, mono-ligand complexes in different protonation states were identified. Dimethylation of the terminal amino group resulted in the formation of vanadium(IV/V) complexes with considerably higher stability. Three of the most stable complexes were also synthesized in solid state and comprehensively characterized. The biological evaluation of the synthesized vanadium complexes in comparison to the metal-free ligands in different human cancer cell lines revealed only minimal influence of the metal ion. Thus, in addition the coordination ability of salicylaldehyde thiosemicarbazone (STSC) to vanadium(IV/V) ions was investigated. The exchange of the pyridine nitrogen of the α(N)-heterocyclic TSCs to a phenolate oxygen in STSC significantly increased the stability of the complexes in solution. Finally, this also resulted in increased cytotoxicity activity of a vanadium(V) complex of STSC compared to the metal-free ligand. PMID:26349014

  14. Vanadium Complexes with Hydrazone or Thiosemicarbazone Ligands as Potential Anti-Mycobacterium tuberculosis Agents.

    PubMed

    de Souza, Paula C; Maia, Pedro I S; de Barros, Heloisa B; Leite, Clarice Q F; Deflon, Victor M; Pavan, Fernando R

    2015-01-01

    Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis (MTB) and still an important public health problem worldwide. Some factors like the emergence of multidrug resistant (MDR) and extensively drug-resistant (XDR) strains make urgent the research of new active compounds. Searching for new inorganic compounds against TB, three new dioxovanadium(V) complexes were obtained upon reaction of [VO(acac)2] with hydrazone and thiosemicarbazone ligands derived from di-2-pyridyl ketone. Spectroscopic studies and X-ray crystallography revealed asymmetrically oxo bridged binuclear complexes of the type [{VO(L(1,2))}2(μ-O)2], involving the hydrazone ligands, while a mononuclear square pyramidal complex of the type [VO2(L(3))] was formed with the thiosemicarbazone ligand. The compounds were tested against M. tuberculosis and three of them, with MICs values between 2.00 and 3.76 μM were considered promising for TB treatment. Such MIC values are comparable or better than those found for some drugs currently used in TB treatment. PMID:24433444

  15. Generating nanoparticles containing a new 4-nitrobenzaldehyde thiosemicarbazone compound with antileishmanial activity.

    PubMed

    Britta, Elizandra Aparecida; da Silva, Cleuza Conceição; Rubira, Adley Forti; Nakamura, Celso Vataru; Borsali, Redouane

    2016-12-01

    Thiosemicarbazones are an important class of compounds that have been extensively studied in recent years, mainly because of their broad profile of pharmacological activity. A new 4-nitrobenzaldehyde thiosemicarbazone compound (BZTS) that was derived from S-limonene has been demonstrated to have significant antiprotozoan activity. However, the hydrophobic characteristic of BZTS limits its administration and results in low oral bioavailability. In the present study, we proposed the synthesis of nanoparticle-based block copolymers that can encapsulate BZTS, with morphological evaluation of the nanoparticle suspensions being performed by transmission and cryo-transmission electronic microscopy. The mean particle sizes of the nanoparticle suspensions were determined by static light and dynamic light scattering (SLS/DLS), and the hydrodynamic radius (Rh) was determined using the Stokes-Einstein equation. The zeta potential (ζ) and polydispersity index (PDI) were also determined. The entrapment encapsulation efficiency of the BZTS nanoparticles was measured by ultraviolet spectrophotometry. In vitro activity of BZTS nanoparticle suspensions against intracellular amastigotes of Leishmania amazonensis and cytotoxic activity were also evaluated. The results showed the production of spherical nanoparticles with varied sizes depending on the hydrophobic portion of the amphiphilic diblock copolymers used. Significant concentration-dependent inhibitory activity against intracellular amastigotes was observed, and low cytotoxic activity was demonstrated against macrophages. PMID:27612813

  16. Synthesis and biological evaluation of some new N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones.

    PubMed

    Pervez, Humayun; Ramzan, Muhammad; Yaqub, Muhammad; Nasim, Faiz-ul-Hassan; Khan, Khalid Mohammed

    2012-05-01

    A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values>2.30x10(-4) M-2.79x10(-4) M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds. PMID:22530899

  17. Cytotoxic gallium complexes containing thiosemicarbazones derived from 9-anthraldehyde: Molecular docking with biomolecules

    NASA Astrophysics Data System (ADS)

    Beckford, Floyd A.; Brock, Alyssa; Gonzalez-Sarrías, Antonio; Seeram, Navindra P.

    2016-10-01

    We have synthesized a trio of gallium complexes bearing 9-anthraldehyde thiosemicarbazones. The complexes were assessed for their anticancer activity and their biophysical reactivity was also investigated. The three complexes displayed good cytotoxic profiles against two human colon cancer cell lines, HCT-116 and Caco-2. The IC50 ranged from 4.7 to 44.1 μM with the complex having an unsubstituted amino group on the thiosemicarbazone being the most active. This particular complex also showed a high therapeutic index. All three complexes bind strongly to DNA via intercalation with binding constants ranging from 7.46 × 104 M-1 to 3.25 × 105 M-1. The strength of the binding cannot be directly related to the level of anticancer activity. The complexes also bind strongly to human serum albumin with binding constants on the order of 104-105 M-1 as well. The complexes act as chemical nucleases as evidenced by their ability to cleave pBR322 plasmid DNA. The binding constants along with the cleavage results may suggest that the extent of DNA interaction is not directly correlated with anticancer activity. The results of docking studies with DNA, ribonucleotide reductase and human serum albumin, however showed that the complex with the best biological activity had the largest binding constant to DNA.

  18. Effect of thiosemicarbazones on corrosion of steel in phosphoric acid produced by wet process

    SciTech Connect

    Khamis, E.; Ameer, M.A.; AlAndis, N.M.; Al-Senani, G.

    2000-02-01

    Corrosion inhibition of steel in phosphoric acid (H{sub 3}PO{sub 4}) by thiosemicarbazide derivatives was studied using different chemical and electrochemical techniques. Protection efficiency up to 99% was obtained with small amounts (10{sup {minus}4} M) of cinnamaldehyde thiosemicarbazone (CTSCN). The order of increasing inhibition efficiency was correlated with the modification of the molecular structure of the inhibitors. Empirical kinetic relationship was obtained describing the experimental data obtained from the different compounds used in this investigation. Potentiodynamic polarization curves indicated that the compounds acted primarily as mixed-type inhibitors. Electrochemical impedance spectroscopy showed that the charge-transfer resistance increased and the capacitance of the double layer decreased with increasing the concentration of the inhibitor in the medium, confirming adsorption process mechanism. At high concentrations (>10{sup 4} M), the capacitance of the double layer leveled off since maximum double-layer thickness was attained. Kinetic-thermodynamic model and Flory-Huggins adsorption isotherm described the experimental findings. Number of active sites, binding constant, and change of free energy were computed for all inhibitors studied. Based on the inhibitor, it was found that each organic molecule replaced one or more adsorbed water molecule from the steel surface. The influence of exposure time on the performance of crotonaldehyde thiosemicarbazone (CrTSCN) was studied. Results showed that the inhibitor performed better with time and at a critical concentration of 5 x 10{sup {minus}4} M.

  19. Lanthanum(III) and praseodymium(III) complexes with isatin thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Rai, Anita; Sengupta, Soumitra K.; Pandey, Om P.

    2005-09-01

    Ten new lanthanum(III) and praseodymium(III) complexes of the general formula Na[La(L) 2H 2O] (Ln = La(III) or Pr(III); LH 2 = thiosemicarbazones) derived from the condensation of isatin with 4-phenyl thiosemicarbazide, 4-(4-chlorophenyl) thiosemicarbazide, 4-(2-nitrophenyl) thiosemicarbazide, 4-(2-bromophenyl) thiosemicarbazide and 4-(2-methylphenyl) thiosemicarbazide, have been synthesized in methanol in presence of sodium hydroxide. The XRD spectra of the complexes were monitored to verify complex formation. The complexes have also been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H and 13C NMR spectral studies. Thermal studies of these complexes have been carried out in the temperature range 25-800 °C using TG, DTG and DTA techniques. All these complexes decompose gradually with the formation of Ln 2O 3 as the end product. The Judd-ofelt intensity parameter, oscillator strength, transition probability, stimulated emission cross section for different transitions of Pr 3+ for 4-phenyl thiosemicarbazones have been calculated.

  20. Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action.

    PubMed

    Djoko, Karrera Y; Paterson, Brett M; Donnelly, Paul S; McEwan, Alastair G

    2014-04-01

    The copper(II) complexes of bis-thiosemicarbazones (Cu(btsc)) such as Cu(atsm) and Cu(gtsm) are neutral, lipophilic compounds that show promise as therapeutics for the treatment of certain neurological diseases and cancers. Although the effects of these compounds have been described at the cellular level, there is almost no information about their biochemical mode of action. In this work, we showed that Cu(atsm) and Cu(gtsm) displayed antimicrobial activities against the human obligate pathogen Neisseria gonorrhoeae that were more than 100 times more potent than Cu(NO3)2 salt alone. Treatment with Cu(btsc) also produced phenotypes that were consistent with copper poisoning, but the levels of intracellular copper were undetectable by ICP MS. We observed that Cu(btsc) interacted with proteins in the cell membrane. Systematic measurements of O2 uptake further demonstrated that treatment with both Cu(atsm) and Cu(gtsm) led to dose-dependent inhibition of respiratory electron transfer processes via succinate and NADH dehydrogenases. These dehydrogenases were not inhibited by a non-btsc source of Cu(II). The results led us to conclude that the biochemical mechanism of Cu(btsc) action is likely more complex than the present, simplistic model of copper release into the cytoplasm. PMID:24435165

  1. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

    PubMed Central

    Goytia, Maira M.; Donnelly, Paul S.; Schembri, Mark A.; Shafer, William M.

    2015-01-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  2. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    PubMed

    Djoko, Karrera Y; Goytia, Maira M; Donnelly, Paul S; Schembri, Mark A; Shafer, William M; McEwan, Alastair G

    2015-10-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  3. Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets--iron, cyclin-dependent kinase (CDK) 2, and CDK9.

    PubMed

    Debebe, Zufan; Ammosova, Tatyana; Breuer, Denitra; Lovejoy, David B; Kalinowski, Danuta S; Kumar, Krishna; Jerebtsova, Marina; Ray, Patricio; Kashanchi, Fatah; Gordeuk, Victor R; Richardson, Des R; Nekhai, Sergei

    2011-01-01

    HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the HIV-1 promoter. Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), and the iron chelator deferasirox (ICL670) inhibits HIV-1 transcription. Here we have analyzed a group of novel di-2-pyridylketone thiosemicarbazone- and 2-benzoylpyridine thiosemicarbazone-based iron chelators that exhibit marked anticancer activity in vitro and in vivo (Proc Natl Acad Sci USA 103:7670-7675, 2006; J Med Chem 50:3716-3729, 2007). Several of these iron chelators, in particular 2-benzoylpyridine 4-allyl-3-thiosemicarbazone (Bp4aT) and 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT), inhibited HIV-1 transcription and replication at much lower concentrations than did 311 and ICL670. Neither Bp4aT nor Bp4eT were toxic after a 24-h incubation. However, longer incubations for 48 h or 72 h resulted in cytotoxicity. Analysis of the molecular mechanism of HIV-1 inhibition showed that the novel iron chelators inhibited basal HIV-1 transcription, but not the nuclear factor-κB-dependent transcription or transcription from an HIV-1 promoter with inactivated SP1 sites. The chelators inhibited the activities of CDK2 and CDK9/cyclin T1, suggesting that inhibition of CDK9 may contribute to the inhibition of HIV-1 transcription. Our study suggests the potential usefulness of Bp4aT or Bp4eT in antiretroviral regimens, particularly where resistance to standard treatment occurs. PMID:20956357

  4. Iron Chelators of the Di-2-pyridylketone Thiosemicarbazone and 2-Benzoylpyridine Thiosemicarbazone Series Inhibit HIV-1 Transcription: Identification of Novel Cellular Targets—Iron, Cyclin-Dependent Kinase (CDK) 2, and CDK9S⃞

    PubMed Central

    Debebe, Zufan; Ammosova, Tatyana; Breuer, Denitra; Lovejoy, David B.; Kalinowski, Danuta S.; Karla, Pradeep K.; Kumar, Krishna; Jerebtsova, Marina; Ray, Patricio; Kashanchi, Fatah; Gordeuk, Victor R.; Richardson, Des R.

    2011-01-01

    HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the HIV-1 promoter. Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), and the iron chelator deferasirox (ICL670) inhibits HIV-1 transcription. Here we have analyzed a group of novel di-2-pyridylketone thiosemicarbazone- and 2-benzoylpyridine thiosemicarbazone-based iron chelators that exhibit marked anticancer activity in vitro and in vivo (Proc Natl Acad Sci USA 103:7670–7675, 2006; J Med Chem 50:3716–3729, 2007). Several of these iron chelators, in particular 2-benzoylpyridine 4-allyl-3-thiosemicarbazone (Bp4aT) and 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT), inhibited HIV-1 transcription and replication at much lower concentrations than did 311 and ICL670. Neither Bp4aT nor Bp4eT were toxic after a 24-h incubation. However, longer incubations for 48 h or 72 h resulted in cytotoxicity. Analysis of the molecular mechanism of HIV-1 inhibition showed that the novel iron chelators inhibited basal HIV-1 transcription, but not the nuclear factor-κB-dependent transcription or transcription from an HIV-1 promoter with inactivated SP1 sites. The chelators inhibited the activities of CDK2 and CDK9/cyclin T1, suggesting that inhibition of CDK9 may contribute to the inhibition of HIV-1 transcription. Our study suggests the potential usefulness of Bp4aT or Bp4eT in antiretroviral regimens, particularly where resistance to standard treatment occurs. PMID:20956357

  5. Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance.

    PubMed

    Pape, Veronika F S; Tóth, Szilárd; Füredi, András; Szebényi, Kornélia; Lovrics, Anna; Szabó, Pál; Wiese, Michael; Szakács, Gergely

    2016-07-19

    There is a constant need for new therapies against multidrug resistant (MDR) cancer. An attractive strategy is to develop chelators that display significant antitumor activity in multidrug resistant cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In this study we used a panel of sensitive and MDR cancer cell lines to evaluate the toxicity of picolinylidene and salicylidene thiosemicarbazone, arylhydrazone, as well as picolinylidene and salicylidene hydrazino-benzothiazole derivatives. Our results confirm the collateral sensitivity of MDR cells to isatin-β-thiosemicarbazones, and identify several chelator scaffolds with a potential to overcome multidrug resistance. Analysis of structure-activity-relationships within the investigated compound library indicates that NNS and NNN donor chelators show superior toxicity as compared to ONS derivatives regardless of the resistance status of the cells. PMID:27161177

  6. Structural and spectral perspectives of a novel thiosemicarbazone synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide

    NASA Astrophysics Data System (ADS)

    Suni, V.; Prathapachandra Kurup, M. R.; Nethaji, Munirathinam

    2006-01-01

    A new thiosemicarbazone, HL is synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide and structurally and spectrochemically characterized. 1H NMR, 13C NMR, COSY, HMQC and IR spectra of the compound are studied and the proton magnetic resonance spectrum reveals some unprecedented observations. The thione form is predominant in the solid state, as supported by the crystal structure and IR data, while a thiol-thione equilibrium is proposed in the solution state by NMR studies. The compound crystallizes into a monoclinic lattice with space group C2/c and the ZE conformation is exhibited by the thiosemicarbazone. Intra- and intermolecular hydrogen-bonding interactions give rise to a two-dimensional packing in the crystal lattice.

  7. Platinum and palladium complexes of thiosemicarbazones derived of 2-acetylthiophene: Synthesis and spectral studies

    NASA Astrophysics Data System (ADS)

    Neto, J. L.; de Lima, G. M.; Beraldo, H.

    2006-03-01

    The reaction of 2-acetylthiophene thiosemicarbazone (2-HATT) and 2-acetylthiophene 4-phenylthiosemicarbazone (2-HAT-4-FT) with Pd(COD)Cl 2 (COD = 1,5-cyclooctadiene) and trans-Pt 2PEt 3Cl 4 yielded four new metal complexes: [Pd(2-HATT)Cl 2] ( 1), [Pd(2-ATT) 2] ( 2), [Pd(2-AT-4-FT)Cl] ( 3) and [Pt(2-ATT)(PEt 3)Cl] ( 4). Apart from compound 3 all the others were characterised by 1H and 13C{ 1H} NMR, infrared spectroscopy, and elemental analysis. Multinuclear NMR experiments of 31P{ 1H} and 195Pt{ 1H} of complex 4 have revealed that the ligand 2-HATT behaves as a bidentate chelating agent towards Pd(COD)Cl 2 and trans-Pt 2PEt 3Cl 4 whereas ligand 2-HAT-4-FT forms a tridentate chelating complex with Pd(COD)Cl 2.

  8. Sequential extraction and determination of copper and nickel with 2,4-dihydroxyacetophenone thiosemicarbazone.

    PubMed

    Reddy, A V; Reddy, Y K

    1986-07-01

    2,4-Dihydroxyacetophenone thiosemicarbazone (DAPT) forms a 1:1 complex with copper(II) which can be extracted into n-butanol or ethyl acetate from acetic acid-sodium acetate (pH 5.0) buffer, and a 1:1 nickel(II) complex which can be extracted into n-butanol from ammonium chloride-ammonia (pH 7.5) buffer. The difference between the pH(1 2 ) values for extraction of the two complexes is 3.4 and this has been exploited for their sequential extraction and determination. The molar absorptivities for the copper and nickel complexes are 1.5 x 10(4)l.mole(-1).cm(-1) at 390 nm and 8.2 x 10(3)l.mole(-1).cm(-1) at 385 nm respectively. The procedure has been applied to the analysis of cupronickel. PMID:18964152

  9. Synthesis, spectral characterization and eukaryotic DNA degradation of thiosemicarbazones and their platinum(IV) complexes

    NASA Astrophysics Data System (ADS)

    Al-Hazmi, G. A.; El-Metwally, N. M.; El-Gammal, O. A.; El-Asmy, A. A.

    2008-01-01

    The condensation products of acetophenone (or its derivatives), salicylaldehyde and o-hydroxy- p-methoxybenzophenone with thiosemicarbazide and ethyl- or phenyl-thiosemicarbazide are the investigated thiosemicarbazones. Their reactions with H 2PtCl 6 produced Pt(IV) complexes characterized by elemental, thermal, mass, IR and electronic spectral studies. The coordination modes were found mononegative bidentate in the acetophenone derivatives and binegative tridentate in the salicylaldehyde derivatives. The complexes were analyzed thermogravimetrically and found highly stable. Some ligands and their complexes were screened against Sarcina sp. and E. coli using the cup-diffusion technique. [Pt( oHAT)(OH)Cl] shows higher activity against E. coli than the other compounds. The degradation power of the tested compounds on the calf thymus DNA supports their selectivity against bacteria and not against the human or related eukaryotic organisms.

  10. Nickel(II) complexes containing thiosemicarbazone and triphenylphosphine: Synthesis, spectroscopy, crystallography and catalytic activity

    NASA Astrophysics Data System (ADS)

    Priyarega, S.; Kalaivani, P.; Prabhakaran, R.; Hashimoto, T.; Endo, A.; Natarajan, K.

    2011-09-01

    Four new Ni(II) complexes of the general formula [Ni(PPh 3)(L)] (L = dibasic tridentate ligand derived from 4-diethylamino-salicylaldehyde and thiosemicarbazide or 4-N-substituted thiosemicarbazide) have been reported. The new complexes have been synthesized and characterized by analytical and spectroscopic (IR, electronic, 1H NMR and 31P NMR) techniques. Molecular structure of one of the complexes has been determined by X-ray crystallography. The complex, [Ni(PPh 3)(L4)] (H 2L4 = thiosemicarbazone prepared from 4-diethylamino-salicylaldehyde and 4-phenylthiosemicarbazide) crystallized in monoclinic space group with two molecules per unit cell and has the dimensions of a = 13.232(6) Å, b = 10.181(5) Å, c = 13.574(7) Å, α = 90°, β = 98.483(2)° and γ = 90°. Catalytic activity of the complexes has been explored for aryl-aryl coupling reaction.

  11. Synthesis of isatin thiosemicarbazones derivatives: In vitro anti-cancer, DNA binding and cleavage activities

    NASA Astrophysics Data System (ADS)

    Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B.; Majid, A. M. S. Abdul

    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (kb = 5.03-33.00 × 105 M-1) for L1-L3 and L5 and (6.14-9.47 × 104 M-1) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.

  12. Synthesis, Spectroscopic, and Antimicrobial Studies on Bivalent Zinc and Mercury Complexes of 2-Formylpyridine Thiosemicarbazone

    PubMed Central

    Chandra, Sulekh; Parmar, Shikha; Kumar, Yatendra

    2009-01-01

    A series of metal complexes of Zn(II) and Hg(II) having the general composition [M(L)2]X2 [where L = 2-formylpyridine thiosemicarbazone; M = Zn(II) and Hg(II); X = Cl−, NO3− and 1/2SO42−] have been prepared and characterized by elemental chemical analysis, molar conductance, and spectral (IR and mass) studies. The IR spectral data suggests the involvement of sulphur and azomethane nitrogen in coordination to the central metal ion. On the basis of spectral studies, a tetrahedral geometry has been assigned for Zn(II) and Hg(II) complexes. The free ligand and its metal complexes have been tested in vitro against a number of microorganisms in order to assess their antimicrobial properties. PMID:19421419

  13. Vibrational spectroscopic studies and computational study of ethyl methyl ketone thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Anoop, M. R.; Binil, P. S.; Suma, S.; Sudarsanakumar, M. R.; Y, Sheena Mary.; Varghese, Hema Tresa; Panicker, C. Yohannan

    2010-04-01

    FT-IR and FT-Raman spectra of ethyl methyl ketone thiosemicarbazone were recorded and analyzed. The crystal structure is also described. The vibrational wavenumbers were computed using HF/6-31G(d) and B3LYP/6-31G(d) basis sets and are assigned with the aid of MOLEKEL program. The first hyperpolarizability, infrared intensities and Raman activities are also reported. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive molecule for future applications in non-linear optics. The geometrical parameters of the title compound obtained from XRD studies are in agreement with the calculated values. The red shift of the NH stretching wavenumber in the infrared spectrum compared to the computed wavenumber indicates the weakening of the N-H bond resulting in proton transfer to the neighbouring sulfur atom.

  14. Spectroscopic study one thiosemicarbazone derivative with ctDNA using ethidium bromide as a fluorescence probe.

    PubMed

    Geng, Shaoguang; Wu, Qing; Shi, Lei; Cui, Fengling

    2013-09-01

    In this study, a thiosemicarbazone derivative (E)-2-((1,4-dihydroxy-9,10-anthraquinone-2-yl)methylene)-N-(4-fluorophenyl)hydrazinecarbothioamide (DAFPT) was synthesized, and the interaction of DAFPT with calf thymus DNA (ctDNA) was explored using ethidium bromide (EB) as a fluorescence probe. The binding mode between DAFPT and ctDNA was investigated by UV absorption spectroscopy, fluorescence spectroscopy and molecular docking. The fluorescence quenching mechanism of EB-ctDNA by DAFPT might be a combined quenching type. Thermodynamic parameters showed that the reaction was spontaneous. According to ionic strength, fluorescence polarization and melting temperature (T(m)) curve results, DAFPT-ctDNA interaction was groove binding. The molecular modeling results indicated that DAFPT could slide into the A-T rich region of ctDNA. PMID:23769721

  15. Synthesis and Biochemical Evaluation of Thiochromanone Thiosemicarbazone Analogues as Inhibitors of Cathepsin L

    PubMed Central

    2012-01-01

    A series of 36 thiosemicarbazone analogues containing the thiochromanone molecular scaffold functionalized primarily at the C-6 position were prepared by chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most promising inhibitors from this group are selective for cathepsin L and demonstrate IC50 values in the low nanomolar range. In nearly all cases, the thiochromanone sulfide analogues show superior inhibition of cathepsin L as compared to their corresponding thiochromanone sulfone derivatives. Without exception, the compounds evaluated were inactive (IC50 > 10000 nM) against cathepsin B. The most potent inhibitor (IC50 = 46 nM) of cathepsin L proved to be the 6,7-difluoro analogue 4. This small library of compounds significantly expands the structure–activity relationship known for small molecule, nonpeptidic inhibitors of cathepsin L. PMID:24900494

  16. Synthesis and spectral studies of platinum metal complexes of benzoin thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Offiong, Offiong E.

    1994-11-01

    The platinum metal chelates of benzoin thiosemicarbazone obtained with Ru(III), Rh(III), Ir(III), Pd(II) and Pt(II) were prepared from their corresponding halide salts. The complexes were characterized by elemental analysis, conductance measurement, IR, Raman, 1H-NMR, 13C-NMR and UV-visible spectra studies. Various ligand field parameters and nephelauxetic parameters were also calculated. The mode of bonding and the geometry of the ligand environment around the metal ion have been discussed in the light of the available data obtained. Complexes of Ru(III), Rh(III) and Ir(III) are six-coordinate octahedral, while Pd(II) and Pt(II) halide complexes are four-coordinated with halides bridging.

  17. Novel aldehyde and thiosemicarbazone derivatives: Synthesis, spectroscopic characterization, structural studies and molecular docking studies

    NASA Astrophysics Data System (ADS)

    Karakurt, Tuncay; Tahtaci, Hakan; Subasi, Nuriye Tuna; Er, Mustafa; Ağar, Erbil

    2016-12-01

    In this study our purpose is that, synthesis and characterization of compounds containing the aldehyde and thiosemicarbazone groups and comparison of the theoretical results with the experimental results. The structures of all synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses techniques. The structure of compound (4) (C9H8N4O2S) was also elucidated by X-ray diffraction analysis. In addition, the theoretical IR spectrum, 1H NMR and 13C NMR chemical shift values, frontier molecular orbital values (FMO) of these molecules were analyzed by using Becke-3- Lee-Yang-Parr (B3LYP) method with LanL2DZ basis set. Finally, molecular docking studies were performed on synthesized compounds using the 4DKI beta-lactam protein structure to determine the potential binding mode of inhibitors.

  18. Synthesis and spectral characterization of acetophenone thiosemicarbazone--a nonlinear optical material.

    PubMed

    Santhakumari, R; Ramamurthi, K; Vasuki, G; Yamin, Bohari M; Bhagavannarayana, G

    2010-08-01

    Acetophenone thiosemicarbazone (APTSC) was synthesized. Solubility of APTSC was determined in ethanol and methanol at different temperatures. Single crystals were grown from ethanol by slow evaporation at room temperature. The grown crystal was subjected to FTIR, Laser-Raman and (1)H NMR spectral analyses to confirm the synthesized compound. Thermal properties were investigated by thermogravimetric and differential thermal analyses. High-resolution X-ray diffractometry (HRXRD) was employed to evaluate the perfection of the grown crystal. The range and percentage of optical transmission was ascertained by recording UV-vis-NIR spectrum. The third order nonlinear optical parameters (nonlinear refractive index and nonlinear absorption coefficient) were derived by the Z-scan technique. PMID:20434945

  19. Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites.

    PubMed

    Fernández, Mariana; Arce, Esteban Rodríguez; Sarniguet, Cynthia; Morais, Tânia S; Tomaz, Ana Isabel; Azar, Claudio Olea; Figueroa, Roberto; Diego Maya, J; Medeiros, Andrea; Comini, Marcelo; Helena Garcia, M; Otero, Lucía; Gambino, Dinorah

    2015-12-01

    Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(η(5)-C5H5)(PPh3)L], with HL=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2=N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50T. cruzi=0.41μM; IC50T. brucei brucei=3.5μM). Moreover, this compound shows excellent selectivity towards T. cruzi (SI>49) and good selectivity towards T. brucei brucei (SI>6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule. PMID:26275470

  20. Gold(III) complexes with ONS-Tridentate thiosemicarbazones: Toward selective trypanocidal drugs.

    PubMed

    Rettondin, Andressa R; Carneiro, Zumira A; Gonçalves, Ana C R; Ferreira, Vanessa F; Oliveira, Carolina G; Lima, Angélica N; Oliveira, Ronaldo J; de Albuquerque, Sérgio; Deflon, Victor M; Maia, Pedro I S

    2016-09-14

    Tridentate thiosemicarbazone ligands with an ONS donor set, H2L(R) (R = Me and Et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-R-3-thiosemicarbazides. H2L(R) reacts with Na[AuCl4]·2H2O in MeOH in a 1:1 M ratio under formation of green gold(III) complexes of composition [AuCl(L(R))]. These compounds represent the first examples of gold(III) complexes with ONS chelate-bonded thiosemicarbazones. The in vitro anti-Trypanosoma cruzi activity against both trypomastigote and amastigote forms (IC50try/ama) of CL Brener strains as well as the cytotoxicity against LLC-MK2 cells of the free ligands and complexes was evaluated. The complex [AuCl(L(Me))] was found to be more active and more selective than its precursor ligand and the standard drug benznidazole with a SItry/ama value higher than 200, being considered as a lead candidate for Chagas disease treatment. Moreover the in vitro activity against the replicative amastigote form (IC50ama) of T. cruzi was additionally investigated revealing that [AuCl(L(Me))] was also more potent than benznidazole still with a similar selectivity index. Finally, docking studies showed that free ligands and complexes interact with the same residues of the parasite protease cruzain but with different intensities, suggesting that this protease could be a possible target for the trypanocidal action of the obtained compounds. PMID:27191616

  1. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy

    PubMed Central

    Yu, Y; Rahmanto, Y Suryo; Richardson, DR

    2012-01-01

    BACKGROUND AND PURPOSE Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led to cardiotoxicity at non-optimal doses. In this study, we examined the in vivo anti-tumour efficacy and tolerability of a new-generation 2-benzoylpyridine thiosemicarbazone iron chelator (2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone; Bp44mT) administered via the oral or i.v. routes. EXPERIMENTAL APPROACH BpT chelators were tested in vitro against human lung cancer cells (DMS-53) and in vivo in DMS-53 tumour xenografts in mice. The toxicity of Bp44mT in vivo and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. KEY RESULTS Administration of Bp44mT by either route resulted in marked dose-dependent inhibition of tumour growth. When administered at 50 mg·kg−1 via oral gavage three times per week for 23 days, the net xenograft growth was inhibited by 75%, compared with vehicle-treated mice. Toxicological examination showed reversible alterations including slight reduction of RBC count, with a decrease of liver and splenic iron levels, which confirmed iron chelation in vivo. Importantly, in contrast to Dp44mT, the chelator-treated mice did not show cardiac histological abnormalities. There was also no significant weight loss in mice, suggesting oral administration of Bp44mT was well tolerated. CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti-tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. PMID:21658021

  2. Crystal structure and photochromism of 1-phenyl-3-methyl-4-benzyl-5-one-pyrazole S-methyl thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Liu, Lang; Jia, Dian-zeng; Ji, Ya-li; Yu, Kai-bei

    2003-07-01

    A new organic photochromic compound containing pyrazolone-ring photochromic functional unit: 1-phenyl-3-methyl-4-benzyl-5-one pyrazole S-methyl thiosemicarbazone (PMBP-smtsc) was synthesized. The photochromic properties and photochemical kinetics of PMBP-smtsc have been studied by UV reflectance spectra under irradiation of 365 nm light. The crystal structure analyses of photocolored product show the photochromism is due to the photoisomerization from enol form to keto form through an intermolecular proton transfer.

  3. Copper(II) complexes with 2-pyridineformamide-derived thiosemicarbazones: Spectral studies and toxicity against Artemia salina

    NASA Astrophysics Data System (ADS)

    Ferraz, Karina O.; Wardell, Solange M. S. V.; Wardell, James L.; Louro, Sonia R. W.; Beraldo, Heloisa

    2009-07-01

    The copper(II) complexes [Cu(H2Am4DH)Cl 2] ( 1), [Cu(H2Am4Me)Cl 2] ( 2), [Cu(H2Am4Et)Cl 2] ( 3) and [Cu(2Am4Ph)Cl] ( 4) with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me), N(4)-ethyl (H2Am4Et) and N(4)-phenyl (H2Am4Ph) derivatives were studied by means of infrared and EPR spectral techniques. The crystal structure of 4 was determined. The studied compounds proved to be toxic to Artemia salina, suggesting that they could present cytotoxic activity against solid tumors. Among the free thiosemicarbazones H2Am4Ph presented higher toxicity than all other compounds, which showed comparable effects. In the case of complexes 2 and 3 toxicity is probably attributable to the complex as an entity or to a synergistic effect involving the thiosemicarbazone and copper. H2Am4Ph and complexes 2 and 3 revealed to be the most promising compounds as potential antineoplasic agents.

  4. Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia.

    PubMed

    Basha, Maram T; Rodríguez, Carlos; Richardson, Des R; Martínez, Manuel; Bernhardt, Paul V

    2014-03-01

    The oxidation of oxyhemoglobin to methemoglobin has been found to be facilitated by low molecular weight iron(III) thiosemicarbazone complexes. This deleterious reaction, which produces hemoglobin protein units unable to bind dioxygen and occurs during the administration of iron chelators such as the well-known 3-aminopyridine-2-pyridinecarbaldehyde thiosemicarbazone (3-AP; Triapine), has been observed in the reaction with Fe(III) complexes of some members of the 3-AP structurally-related thiosemicarbazone ligands derived from di-2-pyridyl ketone (HDpxxT series). We have studied the kinetics of this oxidation reaction in vitro using human hemoglobin and found that the reaction proceeds with two distinct time-resolved steps. These have been associated with sequential oxidation of the two different oxyheme cofactors in the α and β protein chains. Unexpected steric and hydrogen-bonding effects on the Fe(III) complexes appear to be the responsible for the observed differences in the reaction rate across the series of HDpxxT ligand complexes used in this study. PMID:24317633

  5. Synthesis, activity and pharmacophore development for isatin-β-thiosemicarbazones with selective activity towards multidrug resistant cellsa

    PubMed Central

    Hall, Matthew D.; Salam, Noeris K.; Hellawell, Jennifer L.; Fales, Henry M.; Kensler, Caroline B.; Ludwig, Joseph A.; Szakacs, Gergely; Hibbs, David E.; Gottesman, Michael M.

    2009-01-01

    We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β-thiosemicarbazones from our initial study have been validated, and a range of analogs synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1-selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone, and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicty of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity, and aid in directing the search for the mechanism of action of 1. PMID:19397322

  6. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound.

    PubMed

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4'-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID:26360247

  7. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound

    PubMed Central

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4’-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID:26360247

  8. Briefwechsel uber die Partikel "bis" (An Exchange of Letters about the Particle "bis").

    ERIC Educational Resources Information Center

    Ludwig, Horst; Holschuh, Albrecht

    1990-01-01

    A discussion, in the form of an animated letter exchange, argues that, contrary to most current grammatical descriptions, the German particle "bis" should not be viewed as a preposition governing the accusative case. Rather, it is demonstrated that "bis" most often occurs as a proclitic adverb. (16 references) (JTC)

  9. Synthesis, characterization, electrochemical studies, and in vitro antibacterial activity of novel thiosemicarbazone and its Cu(II), Ni(II), and Co(II) complexes.

    PubMed

    Khan, Salman A; Asiri, Abdullah M; Al-Amry, Khalid; Malik, Maqsood Ahmad

    2014-01-01

    Metal complexes were prepared by the reaction of thiosemicarbazone with CuCl2, NiCl2, CoCl2, Cu(OAc)2, Ni(OAc)2, and Co(OAc)2. The thiosemicarbazone coordinates to metal through the thionic sulfur and the azomethine nitrogen. The thiosemicarbazone was obtained by the thiosemicarbazide with 3-acetyl-2,5-dimethylthiophene. The identities of these compounds were elucidated by IR, (1)H, (13)C-NMR, and GC-MS spectroscopic methods and elemental analyses. The antibacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined by using chloramphenicol as reference drug. The results showed that compound 1.1 is better inhibitor of both types of tested bacteria as compared to chloramphenicol. PMID:24523641

  10. Synthesis, Characterization, Electrochemical Studies, and In Vitro Antibacterial Activity of Novel Thiosemicarbazone and Its Cu(II), Ni(II), and Co(II) Complexes

    PubMed Central

    Khan, Salman A.; Asiri, Abdullah M.; Al-Amry, Khalid; Malik, Maqsood Ahmad

    2014-01-01

    Metal complexes were prepared by the reaction of thiosemicarbazone with CuCl2, NiCl2, CoCl2, Cu(OAc)2, Ni(OAc)2, and Co(OAc)2. The thiosemicarbazone coordinates to metal through the thionic sulfur and the azomethine nitrogen. The thiosemicarbazone was obtained by the thiosemicarbazide with 3-acetyl-2,5-dimethylthiophene. The identities of these compounds were elucidated by IR, 1H, 13C-NMR, and GC-MS spectroscopic methods and elemental analyses. The antibacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined by using chloramphenicol as reference drug. The results showed that compound 1.1 is better inhibitor of both types of tested bacteria as compared to chloramphenicol. PMID:24523641

  11. Half-sandwich ruthenium-arene complexes with thiosemicarbazones: Synthesis and biological evaluation of [(η6-p-cymene)Ru(piperonal thiosemicarbazones)Cl]Cl complexes

    PubMed Central

    Dourth, Deidra; Shaloski, Michael; Didion, Jacob; Thessing, Jeffrey; Woods, Jason; Crowell, Vernon; Gerasimchuk, Nikolay; Gonzalez-Sarrías, Antonio; Seeram, Navindra P.

    2011-01-01

    The synthesis and characterization of a number of organometallic ruthenium(II) complexes containing a series of bidentate thiosemicarbazone ligands derived from piperonal is reported. The structure of compounds have been confirmed by spectroscopic analysis (IR and NMR) as well as X-ray crystallographic analysis of [(η6-p-cymene)Ru(pPhTSC)Cl]Cl (4) (pPhTSC is piperonal-N(4)-phenylthiosemicarbazone). The interaction of the complexes ([(η6-p-cymene)Ru(pEtTSC)Cl]Cl) (3) (pEtTSC is piperonal-N(4)-ethylthiosemicarbazone) and 4 with calf thymus DNA, human serum albumin (HSA) and pBR322 plasmid DNA were studied by spectroscopic, gel electrophoresis and hydrodynamic methods. The apparent binding constant for the interaction with DNA was determined to be 3.97 × 103 M−1 and 4.07 × 103 M−1 at 293 K for 3 and 4 respectively. The complexes bind strongly to HSA with binding constants of 2.94 × 104 M−1 and 12.2 × 104 M−1 at 296 K for 3 and 4 respectively. The in vitro anticancer activity of 3 and 4 has been evaluated against two human colon cancer cell line (HCT-116 and Caco-2) with IC50 values in the range 26 – 150 µM. Both 3 and 4 show good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 µM. The proficiency of 3 and 4 to act as antibacterial agents was also evaluated against six pathogenic bacterial strains with the best activity seen against Gram-positive strains. PMID:21666776

  12. Role of Metalation in the Topoisomerase IIα Inhibition and Antiproliferation Activity of a Series of α-Heterocyclic-N4-Substituted Thiosemicarbazones and Their Cu(II) Complexes

    PubMed Central

    Zeglis, Brian M.; Divilov, Vadim; Lewis, Jason S.

    2014-01-01

    The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The CuII(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-IIα at concentrations (0.3–7.2 μM) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-IIα (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7). PMID:21391686

  13. Hormone Anchored Metal Complexes. 1. Synthesis, Structure, Spectroscopy and In Vitro Antitumor Activity of Testosterone Acetate Thiosemicarbazone and its Metal Complexes

    PubMed Central

    Murugkar, Anupa; Unnikrishnan, Bindu; Bhonde, Ramesh; Teat, Simon; Triantafillou, Evangelia; Sinn, Ekkehard

    1999-01-01

    Testosterone acetate thiosemicarbazone (TATSC, 17-β-hydroxyandrost-4-one acetate thiosemicarbazone) was synthesized and characterized by single crystal X-ray structure determination. The copper and platinum complexes of this steroid derivative were synthesized and characterized by spectroscopy and electrochemiatry. The in vitro activity of these compounds against human breast cancer cell line MCF-7 was tested. The highest activity was found for the [Pt(TATSC)Cl1] followed by [Cu(TATSC)Cl2] and the ligand in compariosn with cisplatin. PMID:18472909

  14. Molecular Ordering in Bis(phenylenyl)bithiophenes

    SciTech Connect

    Stokes,M.; Kortan, R.; Rivillon Amy, S.; Katz, H.; Chabal, Y.; Kloc, C.; Siegrist, T.

    2007-01-01

    The crystal structure of phenylene-bithiophene oligomers (PTTP) has been investigated by powder X-ray diffraction measurements and ab initio Monte Carlo modelling. Two new hydroxyl-terminated PTTP powders, 5,5'-bis-4-(6-hydroxyhexyloxy)-phenyl-2,2'-bithiophene and the shorter alkyl chain substituted oligomer 5,5'-bis(4-hydroxyphenyl)-2,2-bithiophene, are compared to single crystals of 5,5-bis(4-ethylphenyl)-2,2'-bithiophene. The new molecules are characterized by a close packed, distorted hexagonal array with tilted short axes in a herringbone-type structure. Neighboring molecules within layers are displaced along the long axis. Modelling the electrostatic potential surface suggests that electrostatic interactions are responsible for the observed herringbone-like ordering. Alkyl chains facilitate a partial mixing through interdigitation of aromatic and aliphatic moieties.

  15. Supramolecular interactions in biologically relevant compounds. 2-Pyrazineformamide thiosemicarbazones and some products of their cyclization

    NASA Astrophysics Data System (ADS)

    Castiñeiras, Alfonso; García-Santos, Isabel; Nogueiras, Silvia; Rodríguez-González, Iria; Rodríguez-Riobó, Raúl

    2014-09-01

    Reaction of 2-cyanopyrazine with thiosemicarbazide or N-methylthiosemicarbazide afforded the (Z)-2-(amino(pyrazin-2-yl)methylene)hydrazinecarbothioamide (HPzAm4DH) and (Z)-2-(amino(pyrazin-2-yl)methylene)-N-methylhydrazine carbothioamide (HPzAm4M), respectively. (2Z,N‧E)-N‧-(4-Oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (HPzAmot, 5) and (2Z,N‧E)-N‧-(3-methyl-4-oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (MPzAmot, 7) have been synthesized from these thiosemicarbazones with chloroacetic or bromoacetic acids, using a conventional synthetic methodology and microwave-assisted organic reaction enhancement. The crystal structures of the thiosemicarbazones and their solvates [HPzAm4DHṡ1/2 MeOH (1), HPzAm4DHṡH2O (2), HPzAm4M (3), HPzAm4Mṡ2H2O (4)] and the 1,3-thiazolidin-4-ones (5 and 7) have been studied by X-ray diffractometry. All of the compounds were characterized by elemental analysis, mass spectrometry, FT-IR and 1H and 13C NMR spectroscopy. Several by-products have also been isolated in a crystalline form, namely 3-((Z,E)-N‧-(4-oxothiazolidin-2-ylidene)carbamohydrazonium-yl)pyrazin-1-ium dibromide monohydrate, (H3PzAmot)Br2ṡH2O (6), 2-((5-(pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)thio)acetic acid, (H2Pz124ttAc) (8), 2-amino-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride monohydrate, (HPz134tda)ClṡH2O (9), and 2-(methylamino)-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride N-methyl-5-(pyrazin-2-yl)-1,3,4-thiadiazol-2-amine solvate, (HMPz134tda)Clṡ(MPz134tda) (10). The structures of these compounds were also analyzed by X-ray diffractometry. The microwave-assisted organic reaction method for synthesis is easy, convenient, and ecofriendly when compared to the traditional synthetic methods. Crystal analysis revealed that the compounds have extended 3D supramolecular networks through high levels of H-bonding and weak molecular interactions between the molecular moieties and solvent molecules. The novel synthons, which are

  16. 40 CFR 721.10714 - Zinc bis(dialkyldithiocarbamate) (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc bis(dialkyldithiocarbamate... Specific Chemical Substances § 721.10714 Zinc bis(dialkyldithiocarbamate) (generic). (a) Chemical substance... zinc bis(dialkyldithiocarbamate) (PMN P-13-260) is subject to reporting under this section for...

  17. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  18. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  19. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  20. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  1. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  2. 40 CFR 721.10508 - Alkene substituted Bis phenol (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkene substituted Bis phenol (generic... Specific Chemical Substances § 721.10508 Alkene substituted Bis phenol (generic). (a) Chemical substance... alkene substituted bis phenol (PMN P-07-161) is subject to reporting under this section for...

  3. 40 CFR 721.10387 - Substituted bis-phenol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted bis-phenol (generic). 721... Substances § 721.10387 Substituted bis-phenol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted bis-phenol (PMN...

  4. 40 CFR 721.10387 - Substituted bis-phenol (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted bis-phenol (generic). 721... Substances § 721.10387 Substituted bis-phenol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted bis-phenol (PMN...

  5. 40 CFR 721.10508 - Alkene substituted Bis phenol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkene substituted Bis phenol (generic... Specific Chemical Substances § 721.10508 Alkene substituted Bis phenol (generic). (a) Chemical substance... alkene substituted bis phenol (PMN P-07-161) is subject to reporting under this section for...

  6. 40 CFR 721.10387 - Substituted bis-phenol (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted bis-phenol (generic). 721... Substances § 721.10387 Substituted bis-phenol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted bis-phenol (PMN...

  7. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  8. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  9. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  10. Bis(2-chloro-1-methylethyl) ether

    Integrated Risk Information System (IRIS)

    Bis ( 2 - chloro - 1 - methylethyl ) ether ; CASRN 108 - 60 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assess

  11. The binding of β-d-glucopyranosyl-thiosemicarbazone derivatives to glycogen phosphorylase: A new class of inhibitors.

    PubMed

    Alexacou, Kyra-Melinda; Tenchiu Deleanu, Alia-Cristina; Chrysina, Evangelia D; Charavgi, Maria-Despoina; Kostas, Ioannis D; Zographos, Spyros E; Oikonomakos, Nikos G; Leonidas, Demetres D

    2010-11-15

    Glycogen phosphorylase (GP) is a promising target for the treatment of type 2 diabetes. In the process of structure based drug design for GP, a group of 15 aromatic aldehyde 4-(β-d-glucopyranosyl)thiosemicarbazones have been synthesized and evaluated as inhibitors of rabbit muscle glycogen phosphorylase b (GPb) by kinetic studies. These compounds are competitive inhibitors of GPb with respect to α-d-glucose-1-phosphate with IC(50) values ranging from 5.7 to 524.3μM. In order to elucidate the structural basis of their inhibition, the crystal structures of these compounds in complex with GPb at 1.95-2.23Å resolution were determined. The complex structures reveal that the inhibitors are accommodated at the catalytic site with the glucopyranosyl moiety at approximately the same position as α-d-glucose and stabilize the T conformation of the 280s loop. The thiosemicarbazone part of the studied glucosyl thiosemicarbazones possess a moiety derived from substituted benzaldehydes with NO(2), F, Cl, Br, OH, OMe, CF(3), or Me at the ortho-, meta- or para-position of the aromatic ring as well as a moiety derived from 4-pyridinecarboxaldehyde. These fit tightly into the β-pocket, a side channel from the catalytic site with no access to the bulk solvent. The differences in their inhibitory potency can be interpreted in terms of variations in the interactions of the aldehyde-derived moiety with protein residues in the β-pocket. In addition, 14 out of the 15 studied inhibitors were found bound at the new allosteric site of the enzyme. PMID:20947361

  12. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators

    PubMed Central

    Akam, Eman A.; Chang, Tsuhen M.; Astashkin, Andrei V.

    2014-01-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is activated for iron coordination following reduction to the thiolate chelator. In glutathione redox buffer, this reduction event occurs at physiological concentrations and half-cell potentials. Consistent with concurrent reduction and activation, higher intracellular thiol concentrations increase cell susceptibility to prochelator toxicity in cultured cancer cells. The reduction of the disulfide switch and intracellular iron chelation are confirmed in cell-based assays using calcein as a fluorescent probe for paramagnetic ions. The resulting low-spin Fe(III) complex is identified in intact Jurkat cells by EPR spectroscopy measurements, which also document a decreased concentration of active ribonucleotide reductase following exposure to the prochelator. Cell viability and fluorescence-based assays show that the iron complex presents low cytotoxicity and does not participate in intracellular redox chemistry, indicating that this antiproliferative chelation strategy does not rely on the generation of reactive oxygen species. PMID:25100578

  13. Ruthenium (II) complexes of thiosemicarbazone: synthesis, biosensor applications and evaluation as antimicrobial agents.

    PubMed

    Yildirim, Hatice; Guler, Emine; Yavuz, Murat; Ozturk, Nurdan; Kose Yaman, Pelin; Subasi, Elif; Sahin, Elif; Timur, Suna

    2014-11-01

    A conformationally rigid half-sandwich organoruthenium (II) complex [(η(6)-p-cymene)RuClTSC(N-S)]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh3)2TSC(N-S)] (2) have been synthesized from the reaction of [{(η(6)-p-cymene)RuCl}2(μ-Cl)2] and [Ru(H)(Cl)(CO)(PPh3)3] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at -0.9V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01-0.5mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. PMID:25280673

  14. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents.

    PubMed

    Altıntop, Mehlika Dilek; Atlı, Özlem; Ilgın, Sinem; Demirel, Rasime; Özdemir, Ahmet; Kaplancıklı, Zafer Asım

    2016-01-27

    New thiosemicarbazone derivatives (1-10) were obtained via the reaction of 4-(naphthalen-1-yl)thiosemicarbazide with fluoro-substituted aromatic aldehydes. The synthesized compounds were evaluated for their in vitro antifungal effects against pathogenic yeasts and molds using broth microdilution assay. Ames and umuC assays were carried out to determine the genotoxicity of the most effective antifungal derivatives. Furthermore, all compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using XTT test. Among these derivatives, 4-(naphthalen-1-yl)-1-(2,3-difluorobenzylidene)thiosemicarbazide (1) and 4-(naphthalen-1-yl)-1-(2,5-difluorobenzylidene)thiosemicarbazide (3) can be identified as the most promising antifungal derivatives due to their notable inhibitory effects on Candida species and no cytotoxicity against NIH/3T3 mouse embryonic fibroblast cell line. According to Ames and umuC assays, compounds 1 and 3 were classified as non-mutagenic compounds. On the other hand, 4-(naphthalen-1-yl)-1-(2,4-difluorobenzylidene)thiosemicarbazide (2) can be considered as the most promising anticancer agent against A549 cell line owing to its notable inhibitory effect on A549 cells with an IC50 value of 31.25 μg/mL when compared with cisplatin (IC50 = 16.28 μg/mL) and no cytotoxicity against NIH/3T3 cells. PMID:26706351

  15. Study on the Interaction between Isatin-β-Thiosemicarbazone and Calf Thymus DNA by Spectroscopic Techniques

    PubMed Central

    Pakravan, Parvaneh; Masoudian, Shahla

    2015-01-01

    The interaction between isatin-β-thiosemicarbazone (IBT) and calf thymus DNA (CT-DNA) was investigated in physiological buffer (pH 7.4) using Neutral Red (NR) dye as a spectral probe by UV–Vis absorption and fluorescence spectroscopy, as well as viscosity measurements. The IBT is stabilized by intercalation in the DNA (K [IBT –DNA] = 1.03×105 M−1), and displaces the NR dye from the NR–DNA complex. The binding constants Kf and number of binding sites (n≈1) of IBT with DNA were obtained by fluorescence quenching method at different temperatures. Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA showed that the reaction is enthalpy-favored and entropy-disfavored. The changes in the base stacking of CT-DNA upon the binding of IBT are reflected in the circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA solution is another evidence to indicate that, IBT is able to be intercalated in the DNA base pairs. PMID:25561917

  16. Spectroscopic analysis, AIM, NLO and VCD investigations of acetaldehyde thiosemicarbazone using quantum mechanical simulations

    NASA Astrophysics Data System (ADS)

    Moorthy, N.; Prabakar, P. C. Jobe; Ramalingam, S.; Govindarajan, M.; Gnanamuthu, S. Joshua; Pandian, G. V.

    2016-08-01

    The prepared Acetaldehyde thiosemicarbazone (ATSC) have been investigated by both the experimental and theoretical methods; through this work, the essentiality of elucidation of molecular fragments source linear and non-linear optical properties was explored. The stability of the structure and entire calculations have been performed on HF and B3LYP methods with 6-311++G(d,p) level of basis set. The Mulliken charge profile, electronic, optical and hyper polarizability analyses have been carried out in order to evaluate nonlinear optical (NLO) performance of the present compound. The exact optical location of the ATSC was determined by executing UV-Visible calculations on TDSCF method. The existence of the molecular group for the inducement and tuning of NLO properties were thoroughly investigated by performing fundamental vibrational investigation. The optical energy transformation among frontier molecular levels has been described in UV-Visible region. The Gibbs energy coefficient of thermodynamic functions was monitored in different temperature and it was found constant irrespective of temperatures. The appearance of different chemical environment of H and C was monitored from the 1H and 13C NMR spectra. The vibrational optical polarization characteristics with respect to molecular composition in the compound have been studied by VCD spectrum. The bond critical point, Laplacian of electron density, electron kinetic energy density and total electron energy density have calculated and analysed using AIM study.

  17. Identification of Semicarbazones, Thiosemicarbazones and Triazine Nitriles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

    PubMed Central

    Schröder, Jörg; Noack, Sandra; Marhöfer, Richard J.; Mottram, Jeremy C.; Coombs, Graham H.; Selzer, Paul M.

    2013-01-01

    Cysteine proteases of the papain superfamily are present in nearly all eukaryotes. They play pivotal roles in the biology of parasites and inhibition of cysteine proteases is emerging as an important strategy to combat parasitic diseases such as sleeping sickness, Chagas’ disease and leishmaniasis. Homology modeling of the mature Leishmania mexicana cysteine protease CPB2.8 suggested that it differs significantly from bovine cathepsin B and thus could be a good drug target. High throughput screening of a compound library against this enzyme and bovine cathepsin B in a counter assay identified four novel inhibitors, containing the warhead-types semicarbazone, thiosemicarbazone and triazine nitrile, that can be used as leads for antiparasite drug design. Covalent docking experiments confirmed the SARs of these lead compounds in an effort to understand the structural elements required for specific inhibition of CPB2.8. This study has provided starting points for the design of selective and highly potent inhibitors of L. mexicana cysteine protease CPB that may also have useful efficacy against other important cysteine proteases. PMID:24146999

  18. Study on the Interaction between Isatin-β-Thiosemicarbazone and Calf Thymus DNA by Spectroscopic Techniques.

    PubMed

    Pakravan, Parvaneh; Masoudian, Shahla

    2015-01-01

    The interaction between isatin-β-thiosemicarbazone (IBT) and calf thymus DNA (CT-DNA) was investigated in physiological buffer (pH 7.4) using Neutral Red (NR) dye as a spectral probe by UV-Vis absorption and fluorescence spectroscopy, as well as viscosity measurements. The IBT is stabilized by intercalation in the DNA (K [IBT -DNA] = 1.03×10(5) M(-1)), and displaces the NR dye from the NR-DNA complex. The binding constants Kf and number of binding sites (n≈1) of IBT with DNA were obtained by fluorescence quenching method at different temperatures. Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA showed that the reaction is enthalpy-favored and entropy-disfavored. The changes in the base stacking of CT-DNA upon the binding of IBT are reflected in the circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA solution is another evidence to indicate that, IBT is able to be intercalated in the DNA base pairs. PMID:25561917

  19. Crystal structures of crotonaldehyde semicarbazone and crotonaldehyde thiosemicarbazone from X-ray powder diffraction data.

    PubMed

    Arfan, Atef; Rukiah, Mwaffak

    2015-02-01

    Crotonaldehyde semicarbazone {systematic name: (E)-2-[(E)-but-2-en-1-yl-idene]hydrazinecarboxamide}, C5H9N3O, (I), and crotonaldehyde thio-semi-carba-zone {systematic name: (E)-2-[(E)-but-2-en-1-yldene]hydra-zinecarbo--thio-amide}, C5H9N3S, (II), show the same E conformation around the imine C=N bond. Compounds (I) and (II) were obtained by the condensation of crotonaldehyde with semicarbazide hydro-chloride and thio-semicarbazide, respectively. Each mol-ecule has an intra-molecular N-H⋯N hydrogen bond, which generates an S(5) ring. In (I), the crotonaldehyde fragment is twisted by 2.59 (5)° from the semicarbazide mean plane, while in (II) the corresponding angle (with the thio-semicarbazide mean plane) is 9.12 (5)°. The crystal packing is different in the two compounds: in (I) inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the bc plane, while weak inter-molecular N-H⋯S hydrogen bonds in (II) link the mol-ecules into chains propagating in [110]. PMID:25878810

  20. Structural, thermal and optical characterization of an organic NLO material—Benzaldehyde thiosemicarbazone monohydrate single crystals

    NASA Astrophysics Data System (ADS)

    Santhakumari, R.; Ramamurthi, K.

    2011-02-01

    Single crystals of the organic NLO material, benzaldehyde thiosemicarbazone (BTSC) monohydrate, were grown by slow evaporation method. Solubility of BTSC monohydrate was determined in ethanol at different temperatures. The grown crystals were characterized by single crystal X-ray diffraction analysis to determine the cell parameters and by FT-IR technique to study the presence of the functional groups. Thermogravimetric and differential thermal analyses reveal the thermal stability of the crystal. UV-vis-NIR spectrum shows excellent transmission in the region of 200-1100 nm. Theoretical calculations were carried out to determine the linear optical constants such as extinction coefficient and refractive index. Further the optical nonlinearities of BTSC have been investigated by Z-scan technique with He-Ne laser radiation of wavelength 632.8 nm. Mechanical properties of the grown crystal were studied using Vickers microhardness tester. Second harmonic generation efficiency of the powdered BTSC monohydrate was tested using Nd:YAG laser and it is found to be ˜5.3 times that of potassium dihydrogen orthophosphate.

  1. 2-Butyl-4-chloroimidazole based substituted piperazine-thiosemicarbazone hybrids as potent inhibitors of Mycobacterium tuberculosis.

    PubMed

    Jallapally, Anvesh; Addla, Dinesh; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas

    2014-12-01

    Here a series of 2-butyl-4-chloroimidazole based substituted piperazine-thiosemicarbazone hybrids were designed by combining three different pharmacophoric fragments in single molecular architecture. 2-Butyl-4-chloro-1-(3-(4-substituted)piperazin-1-yl)propyl)-1H-imidazole-5-carbaldehydes (4a-p) prepared by reacting carboxaldehyde 2 with N-alkyl piperazines 3a-p which were condensed with thiosemicarbazine to give desired compounds 5a-p in very good yields. Among all sixteen compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), two compounds (E)-2-((2-butyl-4-chloro-1-(3-(4-(o-tolyl) piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene)hydrazinecarbothioamide 5e and (E)-2-((2-butyl-4-chloro-1-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene) hydrazine carbothioamide 5f were found to be the most potent antitubercular agents (MIC: 3.13 μg/mL) with low toxicity profile. PMID:25451998

  2. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators.

    PubMed

    Akam, Eman A; Chang, Tsuhen M; Astashkin, Andrei V; Tomat, Elisa

    2014-10-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is activated for iron coordination following reduction to the thiolate chelator. In glutathione redox buffer, this reduction event occurs at physiological concentrations and half-cell potentials. Consistent with concurrent reduction and activation, higher intracellular thiol concentrations increase cell susceptibility to prochelator toxicity in cultured cancer cells. The reduction of the disulfide switch and intracellular iron chelation are confirmed in cell-based assays using calcein as a fluorescent probe for paramagnetic ions. The resulting low-spin Fe(III) complex is identified in intact Jurkat cells by EPR spectroscopy measurements, which also document a decreased concentration of active ribonucleotide reductase following exposure to the prochelator. Cell viability and fluorescence-based assays show that the iron complex presents low cytotoxicity and does not participate in intracellular redox chemistry, indicating that this antiproliferative chelation strategy does not rely on the generation of reactive oxygen species. PMID:25100578

  3. Synthesis and characterization of some novel antimicrobial thiosemicarbazone O-carboxymethyl chitosan derivatives.

    PubMed

    Mohamed, Nadia A; Mohamed, Riham R; Seoudi, Rania S

    2014-02-01

    Three novel thiosemicarbazone O-carboxymethyl chitosan derivatives were obtained via a condensation reaction of thiosemicarbazide O-carboxymethyl chitosan with o-hydroxybenzaldehyde, p-methoxybenzaldehyde, and p- chlorobenzaldehyde respectively. Their structures were characterized by elemental analysis, FTIR, (13)C NMR and X-ray diffraction. The antimicrobial behaviors of the prepared derivatives against three types of bacteria Staphylococcus aureus (S. aureus, RCMBA 2004), Bacillus subtilis (B. subtilis, RCMBA 6005), and Escherichia coli (E. Coli, RCMBA 5003) and three crops-threatening pathogenic fungi Aspergillus fumigatus (A. fumigatus, RCMBA 06002), Geotrichum candidum (G. candidum, RCMB 05098), and Candida albicans (C. albicans, RCMB 05035) were investigated. The results indicated that the antibacterial and antifungal activities of the investigated derivatives are much higher than those of the parent O-carboxymethyl chitosan. They were more potent in case of Gram-positive bacteria than Gram-negative bacteria. The presence of electron withdrawing chlorine atom on the aryl moiety of the aldehyde portion improved greatly antimicrobial activity to be nearly equivalent to the used standard drugs. PMID:24211430

  4. Benzaldehyde Thiosemicarbazone Derived from Limonene Complexed with Copper Induced Mitochondrial Dysfunction in Leishmania amazonensis

    PubMed Central

    Britta, Elizandra Aparecida; Barbosa Silva, Ana Paula; Ueda-Nakamura, Tânia; Dias-Filho, Benedito Prado; Silva, Cleuza Conceição; Sernaglia, Rosana Lázara; Nakamura, Celso Vataru

    2012-01-01

    Background Leishmaniasis is a major health problem that affects more than 12 million people. Treatment presents several problems, including high toxicity and many adverse effects, leading to the discontinuation of treatment and emergence of resistant strains. Methodology/Principal Findings We evaluated the in vitro antileishmanial activity of benzaldehyde thiosemicarbazone derived from limonene complexed with copper, termed BenzCo, against Leishmania amazonensis. BenzCo inhibited the growth of the promastigote and axenic amastigote forms, with IC50 concentrations of 3.8 and 9.5 µM, respectively, with 72 h of incubation. Intracellular amastigotes were inhibited by the compound, with an IC50 of 10.7 µM. BenzCo altered the shape, size, and ultrastructure of the parasites. Mitochondrial membrane depolarization was observed in protozoa treated with BenzCo but caused no alterations in the plasma membrane. Additionally, BenzCo induced lipoperoxidation and the production of mitochondrial superoxide anion radicals in promastigotes and axenic amastigotes of Leishmania amazonensis. Conclusion/Significance Our studies indicated that the antileishmania activity of BenzCo might be associated with mitochondrial dysfunction and oxidative damage, leading to parasite death. PMID:22870222

  5. Structural, thermal and optical characterization of an organic NLO material--benzaldehyde thiosemicarbazone monohydrate single crystals.

    PubMed

    Santhakumari, R; Ramamurthi, K

    2011-02-01

    Single crystals of the organic NLO material, benzaldehyde thiosemicarbazone (BTSC) monohydrate, were grown by slow evaporation method. Solubility of BTSC monohydrate was determined in ethanol at different temperatures. The grown crystals were characterized by single crystal X-ray diffraction analysis to determine the cell parameters and by FT-IR technique to study the presence of the functional groups. Thermogravimetric and differential thermal analyses reveal the thermal stability of the crystal. UV-vis-NIR spectrum shows excellent transmission in the region of 200-1100 nm. Theoretical calculations were carried out to determine the linear optical constants such as extinction coefficient and refractive index. Further the optical nonlinearities of BTSC have been investigated by Z-scan technique with He-Ne laser radiation of wavelength 632.8 nm. Mechanical properties of the grown crystal were studied using Vickers microhardness tester. Second harmonic generation efficiency of the powdered BTSC monohydrate was tested using Nd:YAG laser and it is found to be ∼5.3 times that of potassium dihydrogen orthophosphate. PMID:21186136

  6. β-Cyclodextrin hydrogels for the ocular release of antibacterial thiosemicarbazones.

    PubMed

    Glisoni, Romina J; García-Fernández, María J; Pino, Marylú; Gutkind, Gabriel; Moglioni, Albertina G; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Sosnik, Alejandro

    2013-04-01

    Two types of hydrophilic networks with conjugated beta-cyclodextrin (β-CD) were developed with the aim of engineering useful platforms for the localized release of an antimicrobial 5,6-dimethoxy-1-indanone N4-allyl thiosemicarbazone (TSC) in the eye and its potential application in ophthalmic diseases. Poly(2-hydroxyethyl methacrylate) soft contact lenses (SCLs) displaying β-CD, namely pHEMA-co-β-CD, and super-hydrophilic hydrogels (SHHs) of directly cross-linked hydroxypropyl-β-CD were synthesized and characterized regarding their structure (ATR/FT-IR), drug loading capacity, swelling and in vitro release in artificial lacrimal fluid. Incorporation of TSC to the networks was carried out both during polymerization (DP method) and after synthesis (PP method). The first method led to similar drug loads in all the hydrogels, with minor drug loss during the washing steps to remove unreacted monomers, while the second method evidenced the influence of structural parameters on the loading efficiency (proportion of CD units, mesh size, swelling degree). Both systems provided a controlled TSC release for at least two weeks, TSC concentrations (up to 4000μg/g dry hydrogel) being within an optimal therapeutic window for the antimicrobial ocular treatment. Microbiological tests against P. aeruginosa and S. aureus confirmed the ability of TSC-loaded pHEMA-co-β-CD network to inhibit bacterial growth. PMID:23499082

  7. Synthesis, structure and biological activity of nickel(II) complexes of 5-methyl 2-furfural thiosemicarbazone.

    PubMed

    Jouad, E M; Larcher, G; Allain, M; Riou, A; Bouet, G M; Khan, M A; Thanh, X D

    2001-09-01

    5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)]. PMID:11566328

  8. Structural and biological evaluation of some metal complexes of vanillin-4N-(2-pyridyl) thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Yousef, T. A.; Abu El-Reash, G. M.; Al-Jahdali, M.; El-Rakhawy, El-Bastawesy R.

    2013-12-01

    The synthesis and characterization of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and U(VI)O2 complexes of vanillin-4N-(2-pyridyl) thiosemicarbazone (H2PVT) are reported. Theoretical calculations have been performed to obtain IR spectra of ligand and its complexes using AM1, Zindo/1, MM+ and PM3, methods. The Schiff base and its metal complexes have been screened for antibacterial Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Staphylococcus saprophyticus. H2VPT shows no apparent digestion effect on the egg albumin while Mn(II), Hg(II) and Cu(II) complexes exhibited a considerable digestion effect following the order Cu(II) > Mn(II) > Hg(II). Moreover, Ni(II) and Co(II) complexes revealed strong digestion effect. Fe(II), Mn(II), Cu(II), Zn(II) and Ni(II) acted as metal co- SOD enzyme factors, which are located in different compartments of the cell.

  9. Targeting triple negative breast cancer cells by N3-substituted 9,10-Phenanthrenequinone thiosemicarbazones and their metal complexes

    NASA Astrophysics Data System (ADS)

    Afrasiabi, Zahra; Stovall, Preston; Finley, Kristen; Choudhury, Amitava; Barnes, Charles; Ahmad, Aamir; Sarkar, Fazlul; Vyas, Alok; Padhye, Subhash

    2013-10-01

    Novel N3-substituted 9,10-Phenanthrenequinone thiosemicarbazones and their copper, nickel and palladium complexes are structurally characterized and reported along with the single crystal X-ray structures of three ligands and one nickel complex. All compounds were evaluated for their antiproliferative potential against Triple Negative Breast Cancer (TNBC) cells which have poor prognosis and no effective drugs to treat with. All compounds exhibited antiproliferative activity against these cells. Among the metal complexes evaluated, redox active copper complexes were found to be more potent. The possible mechanism for such enhanced activity can be attributed to the generation of oxidative stress, which was amenable for targeting through metal complexation.

  10. Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal.

    PubMed

    Joselice e Silva, M; Alves, A J; Do Nascimento, S C

    1998-03-01

    Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation to aldehyde using pyridinium dichromate (PDC) and condensation with five N-substituted derivatives of thiosemicarbazide. Tests were performed to evaluate the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6 micrograms/ml, respectively. PMID:9639871

  11. [Spectroscopic studies on the formation of metal complexes and on the protein binding of antiviral thiosemicarbazone derivatives (author's transl)].

    PubMed

    Heinisch, L; Kramarczyk, K; Tonew, M; Hesse, G

    1981-04-01

    The complexation of some thiosemicarbazones and isothiosemicarbazones of isatin and quinolin-2-aldehydes with Cu2+, Zn2+ and Mn2+ ions was spectrometrically investigated. Semiquantitative data, obtained from extinction values, about the relative complexing tendencies within some groups of homologous substances were brought in relation to their antiviral effects and binding to bovine serum albumin. The complexing tendencies were greatest in compounds with methyl substituents and decreased for higher alkyl substituents. whereas the binding to protein increased in the same order. The well-known maxima of the antiviral observed with medium alkyl groups may be explained by a superposition of these effects. PMID:7255526

  12. Conformation and coordination of 1-phenyl-3-methyl-4-benzal-5-pyrazolone thiosemicarbazone: A density functional study

    NASA Astrophysics Data System (ADS)

    Wu, Dongling; Jia, Dianzeng; Liu, Lang; Liu, Anjie

    Density functional theory method has been employed to study the molecular properties of four tautomers and their deprotonated species of 1-phenyl-3-methyl-4-benzal-5-pyrazolone thiosemicarbazone. The solvent effect has been investigated by applying the polarizable continuum model of the self-consistent reaction field theory. The condensed Fukui functions have been calculated to assess the relative reactivity of different sites in the ligands. Molecular electrostatic potential is obtained as an additional molecular descriptor for revealing the regions of the molecular species to which an electrophile would initially be attracted.

  13. Spectral and structural studies of copper(II) complexes of thiosemicarbazones derived from salicylaldehyde and containing ring incorporated at N(4)-position

    NASA Astrophysics Data System (ADS)

    Latheef, Leji; Kurup, Maliyeckal R. Prathapachandra

    2008-06-01

    Mononuclear and binuclear copper(II) complexes ( 1- 8) with two ONS donor thiosemicarbazone ligands {salicylaldehyde 3-hexamethyleneiminyl thiosemicarbazone [H 2L 1] and salicylaldehyde 3-tetramethyleneiminyl thiosemicarbazone [H 2L 2]} have been prepared and physico-chemically characterized. IR, electronic and EPR spectra of the complexes have been obtained. The thiosemicarbazones bind to metal as dianionic ONS donor ligands in all the complexes except in [Cu(HL 1) 2] ( 2) and [Cu(HL 2) 2] ( 6). In compounds 2 and 6 the ligands are coordinated as monoanionic HL - ones. The magnetic susceptibility measurements indicate that all the complexes are paramagnetic. In complex [(CuL 1) 2] ( 1), the magnetic moment value is lower than the expected spin only value. In all the complexes g|| > g⊥ > 2.0023 and G values within the range 2.5-3.5 are consistent with d ground state. The complexes were given the formula as [(CuL 1) 2] ( 1); [Cu(HL 1) 2] ( 2); [CuL 1bpy] ( 3); [CuL 1phen] ( 4); [CuL 1γ-pic]·2H 2O ( 5); [Cu(HL 2) 2] ( 6); [CuL 2py]·3H 2O ( 7); [CuL 2bipy] ( 8). The structure of the compound 8 have been solved by single crystal X-ray crystallography and was found to be distorted square pyramid around copper(II) ion.

  14. Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbazone complexes.

    PubMed

    Adams, Muneebah; de Kock, Carmen; Smith, Peter J; Land, Kirkwood M; Liu, Nicole; Hopper, Melissa; Hsiao, Allyson; Burgoyne, Andrew R; Stringer, Tameryn; Meyer, Mervin; Wiesner, Lubbe; Chibale, Kelly; Smith, Gregory S

    2015-02-01

    A series of ferrocenyl- and aryl-functionalised organosilane thiosemicarbazone compounds was obtained via a nucleophilic substitution reaction with an amine-terminated organosilane. The thiosemicarbazone (TSC) ligands were further reacted with either a ruthenium dimer [(η(6-i)PrC6H4Me)Ru(μ-Cl)Cl]2 or a rhodium dimer [(Cp*)Rh(μ-Cl)Cl]2 to yield a series of cationic mono- and binuclear complexes. The thiosemicarbazone ligands, as well as their metal complexes, were characterised using NMR and IR spectroscopy, and mass spectrometry. The molecular structure of the binuclear ruthenium(ii) complex was determined by single-crystal X-ray diffraction analysis. The thiosemicarbazones and their complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) Plasmodium falciparum strains, displaying activities in the low micromolar range. Selected compounds were screened for potential β-haematin inhibition activity, and it was found that two Rh(iii) complexes exhibited moderate to good inhibition. Furthermore, the compounds were screened for their antitrichomonal activities against the G3 Trichomonas vaginalis strain, revealing a higher percentage of growth inhibition for the ruthenium and rhodium complexes over their corresponding ligand. PMID:25559246

  15. Inhibitory effect of synthetic aromatic heterocycle thiosemicarbazone derivatives on mushroom tyrosinase: Insights from fluorescence, (1)H NMR titration and molecular docking studies.

    PubMed

    Xie, Juan; Dong, Huanhuan; Yu, Yanying; Cao, Shuwen

    2016-01-01

    Three structurally similar aromatic heterocyclic compounds 2-thiophenecarboxaldehyde (a), 2-furaldehyde (b), 2-pyrrolecarboxaldehyde (c) were chosen and a series of their thiosemicarbazone derivatives(1a-3a, 1b-3b and 1c-3c) were synthesized to evaluate their biological activities as mushroom tyrosinase inhibitors. The inhibitory effects of these compounds on tyrosinase were investigated by using spectrofluorimetry, (1)H NMR titration and molecular docking techniques. From the results of fluorescence spectrum and (1)H NMR titration, it was found that forming complexes between the sulfur atom from thiourea and copper ion of enzyme center may play a key role for inhibition activity. Moreover, investigation of (1)H NMR spectra further revealed that formation of hydrogen bond between inhibitor and enzyme may be helpful to above complexes formation. The results were well coincident with the suggestion of molecular docking and obviously showed that 2-thiophone N(4)-thiosemicarbazone (1a), 2-furfuran N(4)-thiosemicarbazone (1b) and 2-pyrrole N(4)-thiosemicarbazone (1c) are potential inhibitors which deserves further investigation. PMID:26213029

  16. Effects of terminal dimethylation and metal coordination of proline-2-formylpyridine thiosemicarbazone hybrids on lipophilicity, antiproliferative activity, and hR2 RNR inhibition.

    PubMed

    Bacher, Felix; Dömötör, Orsolya; Kaltenbrunner, Maria; Mojović, Miloš; Popović-Bijelić, Ana; Gräslund, Astrid; Ozarowski, Andrew; Filipovic, Lana; Radulović, Sinisa; Enyedy, Éva A; Arion, Vladimir B

    2014-12-01

    The nickel(II), copper(II), and zinc(II) complexes of the proline-thiosemicarbazone hybrids 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone (L-Pro-FTSC or (S)-H2L(1)) and 3-methyl-(R)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone (D-Pro-FTSC or (R)-H2L(1)), as well as 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine 4,4-dimethyl-thiosemicarbazone (dm-L-Pro-FTSC or (S)-H2L(2)), namely, [Ni(L-Pro-FTSC-2H)]2 (1), [Ni(D-Pro-FTSC-2H)]2 (2), [Ni(dm-L-Pro-FTSC-2H)]2 (3), [Cu(dm-L-Pro-FTSC-2H)] (6), [Zn(L-Pro-FTSC-2H)] (7), and [Zn(D-Pro-FTSC-2H)] (8), in addition to two previously reported, [Cu(L-Pro-FTSC-2H)] (4), [Cu(D-Pro-FTSC-2H)] (5), were synthesized and characterized by elemental analysis, one- and two-dimensional (1)H and (13)C NMR spectroscopy, circular dichroism, UV-vis, and electrospray ionization mass spectrometry. Compounds 1-3, 6, and 7 were also studied by single-crystal X-ray diffraction. Magnetic properties and solid-state high-field electron paramagnetic resonance spectra of 2 over the range of 50-420 GHz were investigated. The complex formation processes of L-Pro-FTSC with nickel(II) and zinc(II) were studied in aqueous solution due to the excellent water solubility of the complexes via pH potentiometry, UV-vis, and (1)H NMR spectroscopy. The results of the antiproliferative activity in vitro showed that dimethylation improves the cytotoxicity and hR2 RNR inhibition. Therefore, introduction of more lipophilic groups into thiosemicarbazone-proline backbone becomes an option for the synthesis of more efficient cytotoxic agents of this family of compounds. PMID:25391085

  17. New Oxidovanadium Complexes Incorporating Thiosemicarbazones and 1, 10-Phenanthroline Derivatives as DNA Cleavage, Potential Anticancer Agents, and Hydroxyl Radical Scavenger.

    PubMed

    Ying, Peng; Zeng, Pengfei; Lu, Jiazheng; Chen, Hongyuan; Liao, Xiangwen; Yang, Ning

    2015-10-01

    Four novel oxidovanadium(IV) complexes, [VO(hntdtsc)(PHIP)] (1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [VO(hntdtsc)(DPPZ)](2)(DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [VO(satsc)(PHIP)](3) (satsc=salicylaldehyde thiosemicarbazone), and [VO(satsc)(DPPZ)](4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V-FITC/PI assay. The results showed that the growth of human neuroblastoma (SH-SY5Y, SK-N-SH) and human breast adenocarcinoma (MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N-SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor. PMID:25659415

  18. Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis.

    PubMed

    de Melos, Jorge Luiz R; Torres-Santos, Eduardo Caio; Faiões, Viviane dos S; Del Cistia, Catarina de Nigris; Sant'Anna, Carlos Maurício R; Rodrigues-Santos, Cláudio Eduardo; Echevarria, Aurea

    2015-10-20

    A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC₅₀ = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC₅₀ = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. PMID:26375353

  19. Vibrational, NMR and UV-visible spectroscopic investigation and NLO studies on benzaldehyde thiosemicarbazone using computational calculations

    NASA Astrophysics Data System (ADS)

    Moorthy, N.; Prabakar, P. C. Jobe; Ramalingam, S.; Pandian, G. V.; Anbusrinivasan, P.

    2016-04-01

    In order to investigate the vibrational, electronic and NLO characteristics of the compound; benzaldehyde thiosemicarbazone (BTSC), the XRD, FT-IR, FT-Raman, NMR and UV-visible spectra were recorded and were analysed with the calculated spectra by using HF and B3LYP methods with 6-311++G(d,p) basis set. The XRD results revealed that the stabilized molecular systems were confined in orthorhombic unit cell system. The cause for the change of chemical and physical properties behind the compound has been discussed makes use of Mulliken charge levels and NBO in detail. The shift of molecular vibrational pattern by the fusing of ligand; thiosemicarbazone group with benzaldehyde has been keenly observed. The occurrence of in phase and out of phase molecular interaction over the frontier molecular orbitals was determined to evaluate the degeneracy of the electronic energy levels. The thermodynamical studies of the temperature region 100-1000 K to detect the thermal stabilization of the crystal phase of the compound were investigated. The NLO properties were evaluated by the determination of the polarizability and hyperpolarizability of the compound in crystal phase. The physical stabilization of the geometry of the compound has been explained by geometry deformation analysis.

  20. Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities.

    PubMed

    de Oliveira, Jamerson Ferreira; da Silva, Anekécia Lauro; Vendramini-Costa, Débora Barbosa; da Cruz Amorim, Cezar Augusto; Campos, Júlia Furtado; Ribeiro, Amélia Galdino; Olímpio de Moura, Ricardo; Neves, Jorge Luiz; Ruiz, Ana Lúcia Tasca Gois; Ernesto de Carvalho, João; Alves de Lima, Maria do Carmo

    2015-11-01

    A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 μM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 μM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg(-1) chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new anticancer therapies. PMID:26454648

  1. Synthesis, spectroscopic characterization, structural studies and antibacterial and antitumor activities of diorganotin complexes with 3-methoxysalicylaldehyde thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Khandani, Marzieh; Sedaghat, Tahereh; Erfani, Nasrollah; Haghshenas, Mohammad Reza; Khavasi, Hamid Reza

    2013-04-01

    Three organotin(IV) complexes, Ph2Sn(mstsc) (1), Me2Sn(mstsc) (2) and Bu2Sn(mstsc) (3), have been synthesized from reaction of R2SnCl2 (R = Ph, Me and Bu) with 3-methoxysalicylaldehyde thiosemicarbazone (H2mstsc). The synthesized complexes have been characterized by elemental analysis and FT-IR, 1H, 13C and 119Sn NMR spectroscopy. The structures of 2 and 3 have been also confirmed by X-ray crystallography. On the basis of spectral and structural data thiosemicarbazone acts as a tridentate dianionic ligand and coordinates to tin through phenolic oxygen, the azomethine nitrogen and thiolate sulfur atoms. The metal coordination geometry for 2 and 3 is described as distorted square pyramid and the crystal lattices are stabilized by intermolecular hydrogen bands. On the basis of 119Sn NMR data, coordination number of tin retains five in solution. The in vitro antibacterial activity of ligand and its complexes has been evaluated against one Gram-positive and three Gram-negative bacteria. Complex 2 exhibited good activity along with the standard antibacterial drugs. The in vitro cytotoxicities of the synthesized compounds against Jurkat cells were evaluated by the standard WST-1 assay. The activity decreases in the order 3 > 1 > 2 = H2mstsc.

  2. Vibrational, NMR and UV-Visible spectroscopic investigation, VCD and NLO studies on Benzophenone thiosemicarbazone using computational calculations

    NASA Astrophysics Data System (ADS)

    Moorthy, N.; Jobe Prabakar, P. C.; Ramalingam, S.; Periandy, S.; Parasuraman, K.

    2016-04-01

    In order to explore the unbelievable NLO property of prepared Benzophenone thiosemicarbazone (BPTSC), the experimental and theoretical investigation has been made. The theoretical calculations were made using RHF and CAM-B3LYP methods at 6-311++G(d,p) basis set. The title compound contains Cdbnd S ligand which helps to improve the second harmonic generation (SHG) efficiency. The molecule has been examined in terms of the vibrational, electronic and optical properties. The entire molecular behavior was studied by their fundamental IR and Raman wavenumbers and was compared with the theoretical aspect. The molecular chirality has been studied by performing vibrational circular dichroism (circularly polarized infrared radiation). The Mulliken charge levels of the compound ensure the perturbation of atomic charges according to the ligand. The molecular interaction of frontier orbitals emphasizes the modification of chemical properties of the compound through the reaction path. The enormous amount of NLO activity was induced by the Benzophenone in thiosemicarbazone. The Gibbs free energy was evaluated at different temperature and from which the enhancement of chemical stability was stressed. The VCD spectrum was simulated and the optical dichroism of the compound has been analyzed.

  3. Synthesis and spectral feature of benzophenone-substituted thiosemicarbazones and their Ni(II) and Cu(II) complexes

    NASA Astrophysics Data System (ADS)

    El-Asmy, A. A.; Al-Hazmi, G. A. A.

    2009-01-01

    The ligational behavior of 2-hydroxybenzophenone and 2-hydroxy-4-methoxybenzophenone N-substituted thiosemicarbazones towards Ni(II) and Cu(II) ions has been investigated. The isolated complexes were identified by elemental analyses, molar conductance, magnetic moment, IR, UV-vis and ESR spectral studies. The IR spectra indicated that the investigated thiosemicarbazones lost the N 2 proton or the N 2 and OH protons and act as mononegative or binegative tridentate ligands. The ligands containing methoxy group facilitate the deprotonation of OH by resonance more than the SH. Most of the Ni(II) complexes measured subnormal magnetic moments due to square-planar + tetrahedral configuration and supported by the electronic spectra. The percentage of square-planar to tetrahedral was calculated and found in agreement with the ligand splitting energy (10Dq). Also, Cu(II) complexes measured subnormal values due to the interaction between copper centers; the lower the value the higher the interaction. It was found that the substitutent has a noticeable effect on the distortion of the complex. The ESR spectra of some solid Cu(II) complexes at room temperature exhibit g|| > g⊥ > 2.0023 confirming a square-planar structure.

  4. Bridged bis-BODIPYs: their synthesis, structures and properties.

    PubMed

    Kesavan, Praseetha E; Das, Sudipta; Lone, Mohsin Y; Jha, Prakash C; Mori, Shigeki; Gupta, Iti

    2015-10-21

    A series of bis-BODIPYs 1-6 bridged via thiophene, furan, N-alkylcarbazole, triphenyl-amine, para- and meta-phenylene groups have been synthesized and characterized by various spectroscopic techniques. The change in the spectroscopic properties of bis-BODIPYs upon varying the size of spacers was studied. X-ray crystal structures of three bis-BODIPYs containing triphenylamine, para- and meta-phenylene bridges were solved. Intermolecular C(H)π and ππ stacking interactions were observed in solid state structures of three bis-BODIPYs. The dihedral angles between the spacer unit and two boron-dipyrrin units were lower in all three compounds as compared to their corresponding monomers. This suggests increased interactions between the two boron-dipyrrin units in molecules which are in turn reflected in the anodic shifts in their reduction potentials. DFT studies indicated effective electronic interactions between spacers and two boron dipyrrin units in all the bis-BODIPYs. The calculated HOMO-LUMO gap was found to be lower for bis-BODIPY having bulky carbazole spacers and higher for bis-BODIPY having smaller furan spacers. Changing the spacer size clearly affected the spectroscopic properties of the bis-BODIPYs and red shifted absorption and emission maxima were observed for bis-BODIPYs with furan and thiophene spacers as compared to bis-BODIPYs with phenylene or bulky aromatic spacers. PMID:26373792

  5. Bis-iridoid glucosides from Abelia chinensis.

    PubMed

    Tomassini, L; Foddai, S; Serafini, M; Cometa, M F

    2000-07-01

    Seven bis-iridoid glucosides have been isolated from Abelia chinensis and were characterized by having a secoiridoid residue as unit A esterifying a C(10)-iridoid or a delta-lactone iridoid as unit B. Among these, compounds 1-3 are new and correspond to 7-O-acetyllaciniatoside IV, 7-O-acetyllaciniatoside V, and 7-O-acetylabelioside B, respectively. The structures of 1-3 were elucidated by spectral methods. PMID:10924185

  6. Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones.

    PubMed

    Pahontu, Elena; Julea, Felicia; Rosu, Tudor; Purcarea, Victor; Chumakov, Yurie; Petrenco, Petru; Gulea, Aurelian

    2015-04-01

    1-phenyl-3-methyl-4-benzoyl-5-pyrazolone 4-ethyl-thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C₂H₅OH·(1), [Cu(L)₂]·H₂O (2), [Cu(L)(Br)]·H₂O·CH₃OH (3), [Cu(L)(NO₃)]·2C₂H₅OH (4), [VO₂(L)]·2H₂O (5), [Ni(L)₂]·H₂O (6), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, (1) H NMR and (13) C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico-chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) (2, 4), and vanadium(V) (5) complexes have been determined by single-crystal X-ray diffraction. The composition of the coordination polyhedron of the central atom in 2, 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4, it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL-60 cells was tested. PMID:25708540

  7. Nickel(ii) radical complexes of thiosemicarbazone ligands appended by salicylidene, aminophenol and aminothiophenol moieties.

    PubMed

    Kochem, Amélie; Gellon, Gisèle; Jarjayes, Olivier; Philouze, Christian; du Moulinet d'Hardemare, Amaury; van Gastel, Maurice; Thomas, Fabrice

    2015-07-28

    The nickel(ii) complexes of three unsymmetrical thiosemicarbazone-based ligands featuring a sterically hindered salicylidene (1), aminophenol (2) or thiophenol (3) moiety were synthesized and structurally characterized. The metal ion lies in an almost square planar geometry in all the complexes. The cyclic voltammetry (CV) curve of 1 shows an irreversible oxidation wave at E = 0.49 V, which is assigned to the phenoxyl/phenolate redox couple. The CV curves of 2 and 3 display a reversible one-electron oxidation wave (E1/2 = 0.26 and 0.22 V vs. Fc(+)/Fc, respectively) and an one-electron reduction wave (E1/2 = -1.55 and -1.46 V, respectively). The cations 2(+) and 3(+) as well as the anions 2(-) and 3(-) were generated. The EPR spectra of the cations in THF show a rhombic signal at g1 = 2.034, g2 = 2.010 and g3 = 1.992 (2(+)) and g1 = 2.069, g2 = 2.018, g3 = 1.986 (3(+)) that is consistent with a main radical character of the complexes. The difference in anisotropy is assigned to the different nature of the radical, iminosemiquinonate vs. iminothiosemiquinonate. The anions display an isotropic EPR signal at giso = 2.003 (2(+)) and 2.006 (3(+)), which is indicative of a main α-diimine radical character of the compounds. Both the anions and cations exhibit charge transfer transitions of low to moderate intensity in their visible spectrum. Quantum chemical calculations (B3LYP) reproduce both the g-values and Vis-NIR spectra of the complexes. The radical anions readily react with dioxygen to give the radical cations. 2(+) catalyzes the aerobic oxidation of benzyl alcohol into benzaldehyde. PMID:26086684

  8. Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones

    PubMed Central

    Pahontu, Elena; Julea, Felicia; Rosu, Tudor; Purcarea, Victor; Chumakov, Yurie; Petrenco, Petru; Gulea, Aurelian

    2015-01-01

    1-phenyl-3-methyl-4-benzoyl-5-pyrazolone 4-ethyl-thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C2H5OH·(1), [Cu(L)2]·H2O (2), [Cu(L)(Br)]·H2O·CH3OH (3), [Cu(L)(NO3)]·2C2H5OH (4), [VO2(L)]·2H2O (5), [Ni(L)2]·H2O (6), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, 1H NMR and 13C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico-chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) (2, 4), and vanadium(V) (5) complexes have been determined by single-crystal X-ray diffraction. The composition of the coordination polyhedron of the central atom in 2, 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4, it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL-60 cells was tested. PMID:25708540

  9. Antiviral activity of platinum (II) and palladium (II) complexes of pyridine-2-carbaldehyde thiosemicarbazone.

    PubMed

    Varadinova, T; Kovala-Demertzi, D; Rupelieva, M; Demertzis, M; Genova, P

    2001-04-01

    A heterocyclic compound, pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc), and its six metal coordinated bound complexes, three with platinum (II) and three with palladium (II), were studied for their activity against herpes simplex virus 1 (HSV-1) infection in cultured cells. According to their cytotoxicity the compounds were divided into two groups. Group I (cytotoxic compounds) included all three palladium complexes and [Pt(HFoTsc)2] Cl2, with maximum non-toxic concentration (MNC) of 1-10 micromol/l and a 50% cytotoxic concentration (CC50) of 20-100 micromol/l. Group 2 (low cytotoxic compounds) with MNC of 100 micromol/l and CC50 of 548-5820 micromol/l included compounds in the following order: [Pt(HFoTsc)2] Cl2

  10. Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

    PubMed Central

    de Oliveira, Sheilla Andrade; de Oliveira Filho, Gevânio Bezerra; Moreira, Diogo Rodrigo Magalhaes; Gomes, Paulo André Teixeira; da Silva, Anekécia Lauro; de Barros, Andréia Ferreira; da Silva, Aline Caroline; dos Santos, Thiago André Ramos; Pereira, Valéria Rêgo Alves; Gonçalves, Gabriel Gazzoni Araújo; Brayner, Fábio André; Alves, Luiz Carlos; Wanderley, Almir Gonçalves; Leite, Ana Cristina Lima

    2014-01-01

    Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials. PMID:24165185

  11. Maternal BIS Sensitivity, Overprotective Parenting, and Children's Internalizing Behaviors.

    PubMed

    Kiel, Elizabeth J; Maack, Danielle J

    2012-08-01

    Although sensitivity to the Behavioral Inhibition System within Gray's (1970) reinforcement sensitivity theory relates to individuals' own depressive and anxious symptomatology, less is known about how parental BIS sensitivity relates to early indicators of internalizing problems in young children. Moreover, the extent to which this parental characteristic relates to parenting behavior, and children's internalizing problems above and beyond parenting, remains unknown. The current study assessed maternal BIS sensitivity, overprotective parenting, and toddlers' internalizing behaviors in a sample of 91 mothers while controlling for mothers' own internalizing symptomatology. Heightened BIS sensitivity related to both overprotective parenting and internalizing behaviors. Overprotective parenting partially mediated the relation between BIS sensitivity and children's internalizing behaviors, although BIS sensitivity maintained a marginal relation to internalizing behaviors. Maternal BIS sensitivity and toddler internalizing behaviors may represent a shared disposition towards inhibition that is somewhat accounted for by overprotective parenting. PMID:22904590

  12. Efficient transmembrane anion transport mediated by a bis(imidazolyl)-functionalized bis(choloyl) conjugate.

    PubMed

    Li, Zhi; Deng, Li-Qun; Chen, Yun; Wu, Tao; Chen, Wen-Hua

    2016-08-01

    A bis(imidazolyl)-functionalized bis(choloyl) conjugate was synthesized and assessed for its transmembrane anionophoric activity by means of chloride ion selective electrode technique and pyranine assays. The results indicate that under the assay conditions, this conjugate was capable of mediating the symport of proton and anions, presumably via a channel mechanism. In addition, this compound was found to exhibit much higher anionophoric activity than the analogue without imidazolyl groups, revealing the significant role of the imidazolyl groups in the anion transport process. PMID:27289317

  13. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  14. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  15. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  16. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  17. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  18. Trisodium scandium bis­(orthoborate)

    PubMed Central

    Fang, Jinzhi; Zhang, Xinyuan; Yao, Jiyong; Zhang, Guochun; Wang, Kunpeng

    2012-01-01

    Single crystals of tris­odium scandium bis­(orthoborate), Na3Sc(BO3)2, have been obtained by spontaneous crystallization from an Na2O–Sc2O3–B2O3 melt. The crystal structure features a three-dimensional framework composed of planar [BO3]3− groups and distorted ScO6 octa­hedra with Na atoms in the cavities. The Sc atom occupies a special position (Wyckoff position 2b, site symmetry -1) and of the two Na atoms, one occupies a special position (Wyckoff position 2c, site symmetry -1). PMID:22590055

  19. Synthesis of bis(diaryltelluralkoxy)sulfates

    SciTech Connect

    Sadekov, I.D.; Maksimenko, A.A.; Minkin, V.I.

    1987-01-10

    The reactions of diaryltelluroxides with alkylating agents have not been studied with the exception of the treatment with methyl iodide. The authors have shown that reaction of diaryltelluroxides with dialkylsulfates in the corresponding alcohols leads to the previously unknown sigma-telluranes - bis(diaryltelluralkoxy)sulfates - in high yields. The composition and structure of the synthesized compounds were shown by elemental analytical data, IR spectra (band at 1200 cm/sup -1/ for S=O in covalent sulfates), PMR spectra and by their conversion to the corresponding tellurides using formamide (analogously to other sigma-telluranes, Ar/sub 2/TeX/sub 2/ with X = F, Cl Br, or I).

  20. Potential mechanism of the anti-trypanosomal activity of organoruthenium complexes with bioactive thiosemicarbazones.

    PubMed

    Demoro, Bruno; Rossi, Miriam; Caruso, Francesco; Liebowitz, Daniel; Olea-Azar, Claudio; Kemmerling, Ulrike; Maya, Juan Diego; Guiset, Helena; Moreno, Virtudes; Pizzo, Chiara; Mahler, Graciela; Otero, Lucía; Gambino, Dinorah

    2013-06-01

    In the search for new metal-based drugs against diseases produced by trypanosomatid parasites, four organoruthenium(II) compounds [Ru2(p-cymene)2(L)2]X2, where L are bioactive 5-nitrofuryl-containing thiosemicarbazones and X = Cl or PF6, had been previously obtained. These compounds had shown activity on Trypanosoma brucei, the etiological agent of African trypanosomiasis. Because of genomic similarities between trypanosomatides, these ruthenium compounds were evaluated, in the current work, on Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease). Two of them showed significant in vitro growth inhibition activity against the infective trypomastigote form of T. cruzi (Dm28c clone, IC50 = 11.69 and 59.42 μM for [Ru2(p-cymene)2(L4)2]Cl2 and [Ru2(p-cymene)2(L1)2]Cl2, respectively, where HL4 = 5-nitrofuryl-N-phenylthiosemicarbazone and HL1 = 5-nitrofurylthiosemicarbazone), showing fairly good selectivities toward trypanosomes with respect to mammalian cells (J774 murine macrophages). Moreover, [Ru2(p-cymene)2(L2)2]Cl2, where HL2 = 5-nitrofuryl-N-methylthiosemicarbazone, was synthesized in order to evaluate the effect of improved solubility on biological behavior. This new chloride salt showed higher activity against T. cruzi than that of the previously synthesized hexafluorophosphate one (Dm28c clone, IC50 = 14.30 μM for the former and 231.3 μM for the latter). In addition, the mode of antitrypanosomal action of the organoruthenium compounds was investigated. The complexes were not only able to generate toxic free radicals through bioreduction but they also interacted with two further potential parasite targets: DNA and cruzipain, a cysteine protease which plays a fundamental role in the biological cycle of these parasites. The results suggest a "multi-target" mechanism of trypanosomicidal action for the obtained complexes. PMID:23564472

  1. Synthesis, antioxidant activities of the nickel(II), iron(III) and oxovanadium(IV) complexes with N2O2 chelating thiosemicarbazones.

    PubMed

    Bal-Demirci, Tülay; Sahin, Musa; Ozyürek, Mustafa; Kondakçı, Esin; Ulküseven, Bahri

    2014-05-21

    The nickel(II), iron(III) and oxovanadium(IV) complexes of the N2O2 chelating thiosemicarbazones were synthesized using 4-hydroxysalicyladehyde-S-methylthiosemicarbazone and R1-substitute-salicylaldehyde (R1: 4-OH, H) in the presence of Ni(II), Fe(III), VO(IV) ions by the template reaction. The structures of the thiosemicarbazone complexes were characterized by FT-IR, (1)H NMR, elemental, ESI-MS and APCI-MS analysis. The synthesized compounds were screened for their antioxidant capacity by using the cupric reducing antioxidant capacity (CUPRAC) method. Trolox equivalent antioxidant capacity (TEAC) of iron(III) complex, 1c, was measured to be higher than that of the other complexes. Other parameters of antioxidant activity (scavenging effects on •OH, O2(•-) and H2O2) of these compounds were also determined. All the compounds have shown encouraging ROS scavenging activities. PMID:24656797

  2. Structural study of two N(4)-substituted thiosemicarbazones prepared from 1-phenyl-1,2-propanedione-2-oxime and their binuclear nickel(II) complexes

    NASA Astrophysics Data System (ADS)

    Kaminsky, Werner; Jasinski, Jerry P.; Woudenberg, Richard; Goldberg, Karen I.; West, Douglas X.

    2002-05-01

    The crystal structures of the oxime/thiosemicarbazones 1-phenyl-1-{ N(4)-methyl- and 1-phenyl-1-{ N(4)-ethylthiosemicarbazone}-2-oximepropane, H 2Po4M and H 2Po4E, were found to have the oxime and thiosemicarbazone moieties on opposite sides of the carbon-carbon backbone. Intermolecular hydrogen bonding involves the oxime function forming a symmetrical dimer for both compounds. The structures of the binuclear nickel(II) complexes, [Ni(Po4M)] 2 and [Ni(Po4E)] 2, show that bridging by the oximato N-O results in a centrosymmetric arrangement of the two planar nickel centers in each complex. The coordinated thiosemicarbazonato moieties undergo the expected changes in bond distances and angles compared to H 2Po4M and H 2Po4E.

  3. Crystal structures of 5-Bromo-2-hydroxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde, and 2-hydroxynaphthalene-1-carbaldehyde 4-(2-pyridyl) thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Chumakov, Yu. M.; Petrenko, P. A.; Codita, T. B.; Tsapkov, V. I.; Poirier, D.; Gulea, A. P.

    2014-03-01

    5-Bromo-2-hydroxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde, and 2-hydroxynaphthalene-1-carbaldehyde 4-(2-pyridyl) thiosemicarbazones ( I-III, respectively) were synthesized and their crystal structures were determined by X-ray diffraction. All these molecules are almost planar. The presence of bulky substituents at the terminal nitrogen atoms of these molecules does not lead to changes in the conformation of the thiosemicarbazide moiety. Depending on the nature of substituents in the phenol rings, the crystals are composed of either centrosymmetric dimers ( I) or infinite chains ( II and III). In the concentration range of 10-5-10-7 mol/L, thiosemicarbazones I-III selectively inhibit the growth of human myeloid leukemia HL60 cells.

  4. Synthesis, antioxidant activities of the nickel(II), iron(III) and oxovanadium(IV) complexes with N2O2 chelating thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Bal-Demirci, Tülay; Şahin, Musa; Özyürek, Mustafa; Kondakçı, Esin; Ülküseven, Bahri

    The nickel(II), iron(III) and oxovanadium(IV) complexes of the N2O2 chelating thiosemicarbazones were synthesized using 4-hydroxysalicyladehyde-S-methylthiosemicarbazone and R1-substitute-salicylaldehyde (R1: 4-OH, H) in the presence of Ni(II), Fe(III), VO(IV) ions by the template reaction. The structures of the thiosemicarbazone complexes were characterized by FT-IR, 1H NMR, elemental, ESI-MS and APCI-MS analysis. The synthesized compounds were screened for their antioxidant capacity by using the cupric reducing antioxidant capacity (CUPRAC) method. Trolox equivalent antioxidant capacity (TEAC) of iron(III) complex, 1c, was measured to be higher than that of the other complexes. Other parameters of antioxidant activity (scavenging effects on rad OH, O2rad - and H2O2) of these compounds were also determined. All the compounds have shown encouraging ROS scavenging activities.

  5. Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.

    PubMed

    Xie, Wenlin; Xie, Shimin; Zhou, Ying; Tang, Xufu; Liu, Jian; Yang, Wenqian; Qiu, Minghua

    2014-06-23

    A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed. PMID:24819956

  6. A New Thiosemicarbazone-Based Fluorescence "Turn-on" Sensor for Zn(2+) Recognition with a Large Stokes Shift and its Application in Live Cell Imaging.

    PubMed

    Tang, Lijun; Huang, Zhenlong; Zheng, Zhuxuan; Zhong, Keli; Bian, Yanjiang

    2016-09-01

    Selective fluorescence turn on Zn(2+) sensor with long-wavelength emission and a large Stokes shift is highly desirable in Zn(2+) sensing area. We reported herein the synthesis and Zn(2+) recognition properties of a new thiosemicarbazone-based fluorescent sensor L. L displays high selectivity and sensitivity toward Zn(2+) over other metal ions in DMSO-H2O (1:1, v/v, HEPES 10 mM, pH = 7.4) solution with a long-wavelength emission at 572 nm and a large Stokes shift of 222 nm. Confocal fluorescence microscopy experiments demonstrate that L is cell-permeable and capable of monitoring intracellular Zn(2+). Graphical Abstract We report a new thiosemicarbazone-based fluorescent sensor (L) for selective recognition of Zn(2+) with a long wavelength emission and a large Stokes shift. PMID:27333797

  7. Cytotoxic and Antitumour Studies of Acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone and its Transition Metal Complexes

    PubMed Central

    Priya, N. P.; Firdous, A. P.; Jeevana, R.; Aravindakshan, K. K.

    2015-01-01

    Cytotoxic activities of acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone (L2H) and its seven different metal complexes were studied. Of these, IC50 value of the copper complex was found to be 46 μg/ml. Antitumour studies of this copper complex was carried out using Daltons Lymphoma Ascites cell-induced solid tumour model and Ehrlich's Ascites Carcinoma cell-induced ascites tumour model. Administration of the copper complex at different concentrations (10, 5 and 1 mg/kg b. wt) inhibited the solid tumour development in mice and increased the mean survival rate and the life span of Ascites tumour bearing mice in a concentration dependent manner. PMID:26997691

  8. Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells.

    PubMed

    Altintop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Kuş, Gökhan; Oztopcu-Vatan, Pinar; Kabadere, Selda; Kaplancikli, Zafer Asim

    2016-01-01

    Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect. PMID:25826149

  9. Synthesis, stereochemical, structural and biological studies of some 2,6-diarylpiperidin-4-one N(4‧)-cyclohexyl thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Sethukumar, A.; Udhaya Kumar, C.; Agilandeshwari, R.; Arul Prakasam, B.

    2013-09-01

    A new series of 2,6-diarylpiperidin-4-one N(4')-cyclohexyl thiosemicarbazones (13-23) were synthesized by corresponding 2,6-diarylpiperidin-4-ones (1-11) reaction with cyclohexyl thiosemicarbazide (12). The chemical structures were confirmed by means of IR, one and two dimensional NMR, Mass spectra and single crystal X-ray diffraction analysis. Compounds 13-23, exist in chair conformation with equatorial orientation of all the substituents at piperidine ring except the methyl group at C-5 of compounds 21-23 oriented at axial disposition to stabilize the chair conformation. Single crystal X-ray structural analysis of compound 18, evidences that the configuration about Cdbnd N double bond is syn to C-5 carbon (E-form). All the synthesized compounds were screened their biological activity.

  10. Spectroscopic and biological approach of Ni(II) and Cu(II) complexes of 2-pyridinecarboxaldehyde thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Chandra, Sulekh; Raizada, Smriti; Tyagi, Monika; Sharma, Praveen Kumar

    2008-03-01

    Ni(II) and Cu(II) complexes having the general composition [M(L) 2X 2] [where L = 2-pyridinecarboxaldehyde thiosemicarbazone, M = Ni(II) and Cu(II), X = Cl -, NO 3- and 1/2 SO 42-] have been synthesized. All the metal complexes were characterized by elemental analysis, molar conductance, magnetic moment, mass, IR, EPR and electronic spectral studies. The magnetic moment measurements of the complexes indicate that all the complexes are of high-spin type. On the basis of spectral studies an octahedral geometry has been assigned for Ni(II) complexes whereas tetragonal geometry for Cu(II) except [Cu(L) 2SO 4] which posseses five coordinated geometry. The ligand and its metal complexes were screened against phytopathogenic fungi and bacteria in vitro.