142564-62-3

Through systematic structure-activity studies of the 2-benzoylpyridine thiosemicarbazone (HBpT), 2-(3- nitrobenzoyl)pyridine thiosemicarbazone (HNBpT) and dipyridylketone thiosemicarbazone (HDpT) series of iron (Fe) chelators, we identified structural fea

Thiazolidinone derivatives have been previously shown significant anti-cancer activities. Two amino-thiazolidinone complexes, [Pt(HTone)Cl] (1) and [Cu(HTone)Cl] (3) (HTone = (Z)-2-((E)-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one) and one ethyl-modified [Pt(ETone)Cl2] (2) (ETone = (Z)-3-ethyl-2-((E)-(1-(pyridin-2-yl)ethylidene) hydrazono)thiazolidin-4-one)], were designed and synthesized in order to explore novel metal-based antitumor agents. MTT assay indicated that 1 and 3 were markedly cytotoxic to MCF-7, HepG-2 and NCI-H460 tumor cells, superior to both cisplatin and the HTone ligand. Massive dead cells were observed as early as 6 h when treated with 1, indicating rapid action of 1 as compared to that of other compounds. More interestingly, Hoechst 33342 staining and flow cytometry analysis illustrated that only complex 1 could induce obvious cell apoptosis within 12 h, which was associated with the high-expression of Bax and cleavage of caspase-3 from 35 kDa to 17 kDa. By means of ICP-MS assay, we found complex 1 could largely accumulate in tumor cells in a short time. Additionally, complex 1 showed no cross resistance against the cisplatin-resistant cells.

A series of new rhenium(III) complexes, [ReL2]+, where LH = a 2-formylpyridine thiosemicarbazone have been synthesised and characterised. The complexes have been synthesised from the Re(v) starting material [ReOCl3(PPh3)2] and from [ReO4]- in the presence of triphenylphosphine. All of the new compounds have been characterised by X-ray crystallography, NMR and mass spectroscopy. In all cases the Re atom is in a distorted octahedral environment with two tridentate deprotonated thiosemicarbazones binding as monoanionic ligands through the sulfur, pyridyl nitrogen and azamethinic nitrogen in a mer (azomethine nitrogen atoms trans) configuration. Electrochemical measurements show that the complexes undergo two reversible reductions at biologically accessible potentials. Under certain conditions the 2-formylpyridine thiosemicarbazone ligands undergo reductive cleavage of the hydrazinic N-N bond resulting in the formation of a rhenium complex of methyl(2-pyridyl)methyleneimine which has been characterised by X-ray crystallography.

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3- thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors

Dichloro[2-(A,A-dimethylaminomethyl)phenyl-C1,A]gold(iii), [Au(damp-C,A)Cl2] (1), reacts with salicylaldchyde thiosemicarbazone (H2saltsc), vanilline thiosemicarbaezone (Hvantsc), N-methylpyrrole aldehyde thiosemicarbazone (Hmepyrtsc), pyridoxal methylthiosemicarbazone (H2pydoxmetsc), 2-diphenylphosphinobenzaldehyde thiosemicarbazone (HPtsc) or variously substituted acetylpyridine thiosemicarbazones (HapRtsc; R = H, Me, Ph) with cleavage of the Au-N bond and protonation of the dimethylamino group. Compounds of general formulae [Au(Hdamp-C1)CI(L)f (L = Hsaltsc-, vantsc-, mepyrtsc1), [Au(Hdamp-C1)Cl(L)]2+ (L = H2pydoxmetsc) or [Au(Hdamp-C1)(L)]2+ (L = Ptsc-, apRtsc-, R = H, Me, Ph) have been isolated and characterized. The presence of the (T-bonded 2-(dimethylaminomethyl)phenyl ligand is mandatory to prevent reduction of the gold(in) centre. The crystal structures of [Au(Hdanip-C1)CI(HsaItsc)](PF6) (3a), [Au(Hdamp-C')Cl(mepyrtsc)]Cl (3c), [Au(Hdamp-C1)-CI(H2pydo.xtnetsc)]Cl2-MeOH (4), [Au(Hdamp-C1)(apPhtsc)]Cl2-2 MeOH (5c) and [Au(Hdamp-C')(Ptsc)]Cl2-1.5MeOH (6) have been elucidated, showing the gold atoms in distorted square-planar co-ordination environments. The potentially O,N,S-tridentate ligands H2saltsc and H2pydoxmetsc co-ordinate in a bidentate fashion and do not incorporate the OH groups in the chelating framework, whereas HapRtsc or HPtsc co-ordinate in a tridentate manner. Generally, one or more hydrogen atoms of the heterocyclic ligands and/or the NMe2H+ group form hydrogen bridges in the solid state structures. The preliminary results of antiproliferation tests on tumor cells demonstrate the considerable cytotoxicity of these new gold complexes. The Royal Society of Chemistry 2000.

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Three thiosemicarbazone-based platinum(II) complexes [Pt(MH-TSC)Cl] (1), [Pt(ME-TSC)Cl] (2) and [Pt(NH-TSC)2]Cl (3) (MH-TSC = (E)-2-(1-(pyridin-2-yl)ethylidene)hydrazinecarbothioamide, ME-TSC = (E)-N-ethyl-2-(1-(pyridin-2-yl)ethylidene) hydrazinecarbothioamide, NH-TSC = (Z)-2-(amino(pyridin-2-yl)methylene)hydrazinecarbothioamide) were synthesized and structurally characterized. X-ray analyses revealed that 1 and 2 possessed similar a neutral mononuclear unit in which one tridentate TSC ligand and one leaving group (Cl-) coordinated to Pt(II) ion, while 3 was cationic and formed by two NH-TSC ligands surrounding one Pt atom in a meridional arrangement. UV-visible and fluorescence spectra of human serum albumin (HSA) with the complexes displayed that the quenching mechanism of HSA by 1-3 might be a static binding mode. Moreover, synchronous fluorescence experiments proved that 1-3 affected the microenvironment of tryptophan residues of HSA. In addition, the antiproliferative activities against MCF-7 (human breast cancer lines), HepG-2 (human liver hepatocellular carcinoma cell line), NCI-H460 (non-small cell lung cancer lines) and HeLa (human epithelial cervical cancer cell line) were screened for 1-3. Inspiringly, their cytotoxic activity (IC50 = 1.7-9.6 μM) appeared much better than that of cisplatin (IC50 = 5.2-13.5 μM) against different cell lines, respectively. Among them, complex 3 exhibited the strongest inhibition on the viability of all tested cell lines with IC50 values of 1.7-2.2 μM. Inductively-coupled plasma mass spectrometry (ICP-MS) showed that 3 accumulated rapidly in cells and reached intracellular levels of up to 10-fold higher than those determined for 1 and 2. Furthermore, fluorescence microscopic observation and flow cytometric analysis revealed that 1-3 could effectively induce apoptosis of HeLa cells, which were arrested in the S phase after treatment with 1 (30.31%) and 3 (46.96%), and in G2 phase with 2 (20.2%). All the results mentioned above suggest that complexes 1-3 might be efficient antitumor agents.

The present application relates to novel semicarbazones and thiosemicarbazones, to processes for preparing them, to pharmaceutical preparations comprising them, to the use of the novel semicarbazones and thiosemicarbazones for treatment and/or prophylaxis of diseases and to the use thereof for production of a medicament for treatment and/or prophylaxis of diseases, especially of neurodegeneration and age-associated diseases or conditions associated with NAD loss. The present application also provides a method for high throughput screening of NMNAT2 activators.

A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesised, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure–activity relationships. The results of the biological testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a phenyl ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. In addition, the most potent and selective MAO-B inhibitors were evaluated in silico as potential cholinesterase (AChE/BuChE) inhibitors and in vitro for antioxidant activities. The results obtained from molecular modelling studies provided insight into the multiple interactions and structural requirements for the reported MAO inhibitory properties.

In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their inhibitory potential against Mtb, H37Rv, by in vitro assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene] hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and ethyl-2-[(E)-2-[(2- hydroxyphenyl)methylidene]hydrazin-1-yl]-4-methyl-1,3-thiazole-5-carboxylate, 2i showed noticeable inhibitory activity against Mtb, H37Rv with minimum inhibitory concentration (MIC) of 12.5 μM and 25 μM respectively. An attempt has been made to understand the mechanism of action by binding interactions of these molecules with β-ketoacyl-ACP synthase protein through docking studies. The inhibition constants for compounds 4d and 2i were found to be 1.46 μM and 0.177 μM respectively.

The present invention provides a novel class of compounds that disrupt the parasitic infectious life cycle and serve as promising agents for anti-parasitic therapy.

A series of monometallic palladium(II) complexes with thiosemicarbazones and thiobenzoylhydrazones has been synthesized and characterised by spectroscopic methods. The crystal structures of chloro(phenyl 2-pyridyl ketone thiosemicarbazonato)palladium(II) 1a and chloro(phenyl 2-pyridyl ketone thiobenzoylhydrazonato)palladium(II) 2 were also determined. The catalytic activity of the complexes in the homogeneous hydrogenation of phenylacetylene was tested with particular regard to the chemoselectivity from a triple to a double bond. Using chlorocomplexes a high chemoselectivity was always observed. Results of a kinetic study of the hydrogenation of phenylacetylene in the presence of chloro(methyl 2-pyridyl ketone thiosemicarbazonato)palladium(II) 3 as catalyst provided suggestions for the elucidation of the catalytic cycle of the reaction.

The iron(III) complexes of 2-acetylpyridine thiosemicarbazone of the formula Fe(AT-H)2X, where AT-H is the anion of 2-acetylpyridine thiosemicarbazone and X(-) is an anion such as NO3(-), CH(-), Cl(-), N3(-), NCS(-) or NO2(-), have been prepared.They have been characterized by elemental analyses, magnetic measurements, and EPR, UV-visible and IR spectral measurements.These iron(III) complexes are low-spin and have rhombic distortion.The anions of these complexes are strongly associated in solid state and all anions get dissociated in DMF solution except the azide ion.

Based on the antimalarial properties observed for 2-acetylpyridine 4-phenyl-3-thiosemicarbazone (1), an extensive series of related thiosemicarbazones was prepared and tested against Plasmodium berghei in mice. Screening results indicated that the presence of the 2-pyridylethylidene group was critical and that certain phenyl, benzyl, phenethyl, or cycloalkyl groups at N4 of the thiosemicarbazone moiety also contribute to antimalarial activity.