Synthesis and spectroscopic characterization of 13 C4 -labeled 4-cyano-2-oxobutyraldehyde semicarbazone: A metabolite of nitrofurazone.

Nitrofurazone usage in food-producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano-metabolite, 4-cyano-2-oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one- and two-dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier-transform infrared spectroscopy (FT-IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4-[13 C]-cyano-2-oxo- [2, 3, 4-13 C3 ]-butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food-producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real-world problem.

Theoretical Insights into Different Complexation Modes of Dioxovanadium(V) Compounds with Pyridoxal Semicarbazone/Thiosemicarbazone/S-Methyl-iso-thiosemicarbazone Ligands.

Vanadium complexes have gained considerable attention as biologically active compounds. In this contribution, three previously reported dioxovanadium(V) complexes with pyridoxal semicarbazone, thiosemicarbazone, and S-methyl-iso-thiosemicarbazone ligands are theoretically examined. The intermolecular stabilization interactions within crystallographic structures were investigated by Hirshfeld surface analysis. These experimental structures were optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,N,O,S)/def2-TZVP(V) level of theory, and crystallographic and optimized bond lengths and angles were compared. High correlation coefficients and low mean absolute errors between these two data sets proved that the selected level of theory was appropriate for the description of the system. The changes in structures and stability were examined by adding explicit solvent molecules. The Quantum Theory of Atoms in Molecules (QTAIM) was employed to analyze the intramolecular interactions with special emphasis on the effect of substituents. A good correlation between electron density/Laplacian and interatomic distance was found. Through molecular docking simulations towards Bovine Serum Albumin (BSA), the binding affinity of complexes was further investigated. The spontaneity of binding in the active position of BSA was shown. Further experimental studies on this class of compounds are advised.

A novel palladium complex with a coumarin-thiosemicarbazone hybrid ligand inhibits Trypanosoma cruzi release from host cells and lowers the parasitemia in vivo.

In this work, two analogous coumarin-thio and semicarbazone hybrid compounds were prepared and evaluated as a potential antichagasic agents. Furthermore, palladium and platinum complexes with the thiosemicarbazone derivative as ligand (L1) were obtained in order to establish the effect of metal complexation on the antiparasitic activity. All compounds were fully characterized both in solution and in solid state including the resolution of the crystal structure of the palladium complex by X-ray diffraction methods. Unexpectedly, all experimental and theoretical characterizations in the solid state, demonstrated that the obtained palladium and platinum complexes are structurally different: [PdCl(L1)] and [PtCl2(HL1)]. All the studied compounds lower the proliferation of the amastigote form of Trypanosoma cruzi while some of them also have an effect on the trypomastigote stage. Additionally, the compounds inhibit T. cruzi release from host cells in variable extents. The Pd compound presented a remarkable profile in all the in vitro experiments, and it showed no toxicity for mammalian cells in the assayed concentrations. In this sense, in vivo experiments were performed for this compound using an acute model of Chagas disease. Results showed that the complex significantly lowered the parasite count in the mice blood with no significant toxicity.

Facile synthesis of 14 C-nitrofurazone from 14 C-urea.

The veterinary drug nitrofurazone (5-nitro-2-furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food-producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone-specific marker analyte which requires conducting nitrofurazone metabolism studies in food-producing animals. The use of carbon-14 labeled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled nitrofurazone that incorporates 14 C- carbon at the semicarbazide moiety. The method incorporates 14 C-carbon via employing readily available and more economically affordable [14 C]-urea compared with [14 C]-semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5-nitro-2-furaldehyde [14 C]-semicarbazone from 14 C-urea. The developed method involves monoamination of [14 C]-urea followed by a condensation reaction with 5-nitro-2-furaldehyde to produce 5-nitro-2-furaldehyde [14 C]-semicarbazone in 85% yield with greater than 98% radiochemical purity.

Synthesis and evaluation of novel thiosemicarbazone and semicarbazone analogs with both anti-proliferative and anti-metastatic activities against triple negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer with high mortality and recurrence rates. Hecogenin, a steroidal sapogenin, is reported as a potential anti-tumor agent against breast cancer. However, the moderate activity limits its further application in clinical. With the aim to identify novel analogues that are especially efficacious in therapy of TNBC, a series of novel hecogenin thiosemicarbazone and semicarbazone derivatives were designed, synthesized and biologically evaluated. Screening of cytotoxicity revealed that 4c could potently inhibit the proliferation of breast cancer cells (MCF-7 and MDA-MB-231 cells), lung cancer cells (A549) and colon cancer cells (HT-29) at low µM level. Importantly, further mechanism studies indicated the ability of 4c in inducing apoptosis of MDA-MB-231 cells by arresting the cell cycle. Moreover, 4c notably suppressed the migration and invasion of MDA-MB-231 cells compared to its parent hecogenin at the equal concentration.

Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways.

Two new series of betulin derivatives with semicarbazone (7a-g) or thiosemicarbazone (8a-g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 µM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.

Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones.

Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anticancer activity. Derivatives were tested in vitro against 5 human tumor cell lines, and many of these showed higher cytotoxicity than parthenolide. Five compounds were further studied for their antitumor activity in mice. The in vivo result indicated that compound 4d showed both promising antitumor activity against mice colon tumor and small side effects on immune systems. The cell apoptosis and cell cycle distribution of compound 4d were also studied. Molecular docking studies revealed multiple interactions between 4d and NF-κB. Our findings demonstrate the potential of semicarbazones as a promising type of compounds with anticancer activity.

Interplay between Polymorphism and Isostructurality in the 2-Fur- and 2-Thenaldehyde Semi- and Thiosemicarbazones.

The four compounds, namely: 5-nitro-2-furaldehyde thiosemicarbazone (1); 5-nitro-2-thiophene thiosemicarbazone (2); 5-nitro-2-furaldehyde semicarbazone (3); and 5-nitro-2-thiophene semicarbazone (4) were synthesized and crystallized. The three new crystal structures of 1, 2, and 4 were determined and compared to three already known crystal structures of 3. Additionally, two new polymorphic forms of 1 solvate were synthesized and studied. The influence of the exchange of 2-thiophene to 2-furaldehyde as well as thiosemicarbazone and semicarbazone on the self-assembly of supramolecular nets was elucidated and discussed in terms of the formed synthons and assemblies accompanied by Full Interaction Maps analysis. Changes in the strength of IR oscillators caused by the molecular and crystal packing effects are described and explained in terms of changes of electron density.

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies.

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a-g) or thiosemicarbazone (7h-k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 µM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses.

Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed a large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series of (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl benzimidazoles previously reported by us, thereby evaluating the influence of the modification on the antiviral activity. Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved to be the most effective antiviral agents, able to reach the potency profile of the licensed drug ribavirin. The molecular docking analysis explained the SAR of these compounds around their binding mode to the target RSV F protein, revealing the key contacts for further assessment. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses.

Design, synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents.

A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precursor selenochroman-4-ones, the hybrid molecules in this study showed significant improvement in antifungal activities. Notably, compound B8 showed significant antifungal activity against other strains excluding Aspergillus fumigatus (0.25 µg/mL on Candida albicans, 2 µg/mL on Cryptococcus neoformans, 8 µg/mL on Candida zeylanoides and 2 µg/mL on fluconazole-sensitive strains of Candida albicans). Moreover, compounds B8, B9 and C2 also displayed most potent activities against four fluconazole-resistance strains. Especially the MIC values of the hybrid molecule B8 against fluconazole-resistant strains were in the range of 0.5-2 µg/mL. Therefore, the molecular hybridization approach in this study provided new ideas for the development of antifungal drug.

Synthesis and SPAR exploration of new semicarbazone-triazole hybrids in search of potent antioxidant, antibacterial and antifungal agents.

A new series of semicarbazone-triazole hybrid derivatives have been synthesized by condensation between heterocyclic aldehydes and the commercial semicarbazide hydrochloride. The in vitro antioxidant activity of these species was tested using 1,1-diphenyl-2-picrylhydrazyl radical, 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays and their antimicrobial activity against different microbial strains was carried out. Furthermore, molecular properties prediction and drug likeness were also determinated using Molinspiration. Among such derivatives, compounds (E)-2-(4-((1-(2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine carboxamide (4c), and (E)-2-(4-((1-(2-methoxyphenyl)-1-H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine-carboxamide (4e) exhibit excellent scavenging ability, especially with IC50 = 1.57 ± 1.66 mg/mL (4c) and IC50 = 1.82 ± 0.15 mg/mL (4e) with 1,1-diphenyl-2-picrylhydrazyl radical and IC50 = 1.90 ± 1.33 mg/mL (4c) with 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) as compared to the standards butylhydroxytoluene (IC50 = 1.60 ± 1.98 mg/mL) and Trolox (IC50 = 1.45 ± 1.33 mg/mL), respectively. The antimicrobial assay results, show that compounds 4c and 4e highlighted the most interesting profile with the potent activity was obtained against S. enteritidis (1.56-fold) and then M. luteus (1.45-fold) which are significantly higher than the positive control, chloramphenicol. By the other hand, the synthesized semicarbazone derivatives met the Lipinski's rule criteria by presenting good drug likeness and bioactivity scores. The structure-property-activity relationships have been carried out in order to determine the effect of various substituents on the molecular and the biological properties. All these investigations confirm that our synthetic semicarbazone can be explored for generating new potential drug with good oral bioavailability.

Semicarbazone derivatives as promising therapeutic alternatives in leishmaniasis.

In the present study, we investigated the in vitro and in vivo leishmanicidal activity of synthetic compounds, containing a semicarbazone scaffold as a peptide mimetic framework. The leishmanicidal effect against amastigotes of Leishmania amazonensis was also evaluated at concentration of 100 µM-0.01 nM. The derivatives 2e, 2f, 2g and 1g, beyond the standards miltefosine and pentamidine, significantly diminished the number of L. amazonensis amastigotes in macrophages. These derivatives were also active against amastigotes of L. braziliensis. As 2g presented potent leishmanicidal activity against the amastigotes of L. amazonensis in macrophages, we also investigated the in vivo leishmanicidal activity of this compound against L. amazonensis. Approximately 105L. amazonensis promastigotes were subcutaneously inoculated into the dermis of the right ear of BALB/c mice, which were subsequently treated with 2g (p.o. or i.p.), miltefosine (p.o.) or glucantime (i.p.) at 30 µmol/kg/day x 28 days. Thus, a similar reduction in the lesion size was observed after the administration of 2g through oral (63.7 ±â€¯10.1%) and intraperitoneal (61.8 ±â€¯3.7%) routes. A larger effect was observed after treatment with miltefosine (97.7 ±â€¯0.4%), and glucantime did not exhibit activity at the dose administered. With respect to the ear parasite load, 2g diminished the number of parasites by p.o. (30.5 ±â€¯5.1%) and i.p. (33.3 ±â€¯4.3%) administration. In addition, 2g induced in vitro apoptosis, autophagy and cell cycle alterations on L. amazonensis promastigotes. In summary, the derivative 2g might represent a lead candidate for antileishmanial drugs, as this compound displayed pronounced leishmanicidal activity.

Semicarbazone Derivatives Bearing Phenyl Moiety: Synthesis, Anticancer Activity, Cell Cycle, Apoptosis-Inducing and Metabolic Stability Study.

A series of semicarbazone derivatives bearing phenyl moiety were synthesized and evaluated for the vitro anticancer activities in four human cancer cell lines (human colon cancer (HT29), human neuro-blastoma (SK-N-SH), human breast cancer (MDA-MB-231), and human gastric cancer (MKN45)). Biological evaluation led to the identification of 11q and 11s, which showed excellent anticancer activities against tested cancer cell lines with IC50 values ranging from 0.32 to 1.57 µM, respectively, while exhibiting weak cytotoxicity on the normal cells (human umbilical vein endothelial cell (HUVEC)). Flow cytometric assay for cell cycle and apoptosis revealed that 11q and 11s caused an arrest in the Sub-G1 cell cycle and inhibited proliferation of cancer cells by inducing apoptosis in a dose-dependent manner. Further enzymatic assay suggested that 11q and 11s could significantly activated procaspase-3 to caspase-3. Metabolic stability study indicated that 11q and 11s showed moderate stability in vitro in human and rat liver microsomes. In view of promising pharmacological activities of 11q and 11s, which had emerged as the valuable lead for further development in the treatment for cancer.

Design, synthesis, and docking studies of quinazoline analogues bearing aryl semicarbazone scaffolds as potent EGFR inhibitors.

Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o and 10a-o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit µM to nanomole range. Two of them are equal to more active than positive control afatinib against one or more cell lines. The most promising compound 9o showed the best activity against A549, HepG2, MCF-7 and PC-3 cancer cell lines and EGFR kinase, with the IC50 values of 1.32±0.38µM, 0.07±0.01µM, 0.91±0.29µM and 4.89±0.69µM, which were equal to more active than afatinib (1.40±0.83µM, 1.33±1.28µM, 2.63±1.06µM and 3.96±0.59µM), respectively. Activity of the most promising compound 9o (IC50 56nM) against EGFR kinase was slightly lower to the positive compound afatinib (IC50 1.6nM) but more active than reference staurosporine (IC50 238nM). The result of flow cytometry, with the dose of compound 9o increasing, which indicated the compound 9o could induce remarkable apoptosis of A549 and cells in a dose dependent manner. Structure-activity relationships (SARs) and docking studies indicated that replacement of the cinnamamide group by aryl semicarbazone scaffolds slightly decreased the anti-tumor activity. The results suggested that hydroxy substitution at C-4 had a significant impact on the activity and replacement of the tetrahydrofuran group by methyl moiety was not beneficial for the activity.

Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors.

In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that most compounds exhibited moderate-to-excellent activity against HT-29, MKN-45, A549 cancer cell lines and relative poor potency toward MDA-MB-231 cell as well as hardly any cytotoxicity in normal PBL cell. Eleven compounds were further examined for their inhibitory activity against c-Met kinase and three compounds (23h, 23n and 26a) demonstrated good inhibitory activity. This work resulted in the discovery of a potent c-Met inhibitor 23n, bearing 2-hydroxy-3-allylphenyl group at R(2) moiety, as a valuable lead molecule, which possessed remarkable cytotoxicity and high selectivity against A549 and HT-29 cell lines with IC50 values of 11 nM and 27 nM. Besides, it displayed excellent c-Met kinase inhibition on a single-digital nanomolar level (IC50=1.54 nM). Meanwhile, the results from preliminarily in vivo study reflected that compound 23n showed promising overall PK profiles, consistent with the efficacy in both MKN-45 and HT-29 tumor xenograft mice model. These results clearly indicated that compound 23n is a potent and highly selective c-Met inhibitor and its favorable in vitro and in vivo profiles warrant further investigation.

The use of dialdehyde starch derivatives in the phytoremediation of soils contaminated with heavy metals.

Products of the reaction between dialdehyde starch and Y-NH2 compounds (e.g. semicarbazide or hydrazine) are effective ligands for metal ions. The usefulness of these derivatives was tested in the experiment, both in terms of the immobilization of heavy metal ions in soil and the potential application in phytoextraction processes. The experimental model comprised maize and the ions of such metals as: Zn(II), Pb(II), Cu(II), Cd(II), and Ni(II). The amount of maize yield, as well as heavy metal content and uptake by the aboveground parts and roots of maize, were studied during a three-year pot experiment. The results of the study indicate the significant impact of heavy metals on reduced yield and increased heavy metal content in maize. Soil-applied dialdehyde starch derivatives resulted in lower yields, particularly disemicarbazone (DASS), but in heavy metal-contaminated soils they largely limited the negative impact of these metals both on yielding and heavy metal content in plants, particularly dihydrazone (DASH). It was demonstrated that the application of dihydrazone (DASH) to a soil polluted with heavy metals boosted the uptake of Zn, Pb, Cu, and Cd from the soil, hence there is a possibility to use this compound in the phytoextraction of these metals from the soil. Decreased Ni uptake was also determined, hence the possibility of using this compound in the immobilization of this metal. The study showed that dialdehyde starch disemicarbazone was ineffective in the discussed processes.

Crystal structure of 1-(4-formyl-benzyl-idene)thio-semicarbazone.

The asymmetric unit of the title compound, C9H9N3OS, contains two approximately planar mol-ecules (r.m.s. deviations for 14 non-H atoms = 0.094 and 0.045 Å), with different conformations. In one of them, the C=O group is syn to the S atom and in the other it is anti. Each mol-ecule features an intra-molecular N-H⋯N hydrogen bond, which generates an S(5) ring. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯S hydrogen bonds, generating discrete networks; the syn mol-ecules form [010] chains and the anti mol-ecules form (100) sheets.

Crystal structure of cis-bis-[4-phenyl-2-(1,2,3,4-tetra-hydro-naphthalen-1-yl-idene)hydrazinecarbo-thio-amidato-κ(2) N (1),S]nickel(II) monohydrate tetra-hydro-furan disolvate.

The reaction of Ni(II) acetate tetra-hydrate with the ligand 4-phenyl-2-(1,2,3,4-tetra-hydro-naphthalen-1-yl-idene)hydrazinecarbo-thio-amide in a 2:1 molar ratio yielded the title compound, [Ni(C16H16N3S)2]·2C4H8O·H2O. The deprotonated ligands act as N,S-donors, forming five-membered metallacycles with the metal ion exhibiting a cis coordination mode unusual for thio-semicarbazone complexes. The Ni(II) ion is four-coordinated in a tetra-hedrally distorted square-planar geometry. Trans-arranged anagostic C-H⋯Ni inter-actions are observed. In the crystal, the complex mol-ecules are linked by water mol-ecules through N-H⋯O and O-H⋯S hydrogen-bonding inter-actions into centrosymmetric dimers stacked along the c axis, forming rings of graph-set R 4 (4)(12). Classical O-H⋯O hydrogen bonds involving the water and tetra-hydro-furan solvent mol-ecules as well as weak C-H⋯π inter-actions are also present.

Crystal structure of 1-(4-formyl-benzyl-idene)-4-methyl-thio-semicarbazone.

The structure of the title compound, C10H11N3OS, comprises an approximately planar mol-ecule, with the r.m.s. deviation for the 15 non-H atoms being 0.089 Å. The conformation about the imine bond is E and an intra-molecular N-H⋯N hydrogen bond is evident. Mol-ecules are linked into a supra-molecular chain along the b axis by N-H⋯S hydrogen bonds.