Thiosemicarbazone Moiety Research Articles

Molecular and supramolecular properties of nitroaromatic thiosemicarbazones: Synthesis, spectroscopy, X-ray structure elucidation and DFT calculations

The reactions of 6-nitropiperonal with H2NNHC(S)NHR, R = Me, Et, Ph or H, afforded four nitroaromatic thiosemicarbazones 1–4, respectively. 1–4 were characterized by elemental analysis (CHN), FTIR, and 1H and 13C{1H} NMR spectroscopy. In addition, the crystal structures of 2 and 3 were determined by single-crystal X-ray diffraction. Our X-ray structural results have shown that the nitropiperonal and thiosemicarbazone moieties exhibit an almost coplanar arrangement for both 2 and 3. Moreover, they establish 2-D networks along the [111] base vector by means of classical and nonclassical hydrogen bonds. Electronic and spectroscopic properties of 1–4 were investigated at the DFT B3LYP/6-311G** level of calculation. The CS group of 1–4 constitutes a nucleophilic region, whereas the NO2 group defines an electrophilic centre, as expected. Furthermore, a DFT vibrational analysis of 4 allowed a reliable assignment of the thiosemicarbazone-based vibrations. Also, a good agreement between theoretical and experimental 13C chemical shift values was obtained for 1–4.

Novel inhibitors of tyrosinase produced by the 4-substitution of TCT.

We synthesized a series of 4- or 5-functionalized TCT derivatives (1-12) and investigated their inhibitory activities and mechanisms on tyrosinase by using Spectrofluorimetry, 1H and 13C NMR titration and IR spectra. The results of the fluorescence spectra and NMR titrations showed that the thiosemicarbazone moiety formed complexes with copper ions in the active center of the enzyme and played an important role in inhibiting the activities of the target compounds. The 5-functionalization decreased the inhibitory activity, but the 4-functionalization with a methoxyacetyl group enhanced the inhibitory activity, in which a strong auxiliary vicinity synergistic effect from the methoxyacetyl group strengthens and promotes the formation of complexes between the sulfur atoms of the inhibitor and the dicopper nucleus of tyrosinase. We concluded that the appropriate 4-functionalization improved the inhibitory activity of the modifier, and that 4-methoxyacetyl -TCT is promising for the inhibition of tyrosinase.

Синтез и противомикробная активность производных 4-формилфенил-N-фенилкарбамата

Реакциями [3+2]-циклоприсоединения и конденсации на основе 4-формилфенил-N-фенилкарбамата получены новые производные фенилкарбаматов c изоксазольным, нитрофурановым, тиосемикарбазонным, изоникотиноилгидразидным и пиридиновым фрагментами. Изучена их противомикробная активность в отношении музейных штаммов грамположительных бактерий Staphilococcus aureus 209-Р, Streptococcus pneumoniae, грамотрицательных бактерий E. coli O18, Pseudomonas aeruginosa 165, а также культур Micrococcus, выделенных из организма человека. Наиболее активными среди них являются производные с изоксазольным, нитрофурановым и гидразидным фрагментами.

Substituted N-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro.

A library of hybrid molecules bearing thioglycoluril and (hetero)aromatic aldehyde thiosemicarbazone moieties was synthesized via a tandem hydrazone formation-ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (hetero)aromatic aldehydes. All synthesized compounds were tested for their cytotoxic activity against rhabdomyosarcoma, A549, and MS human cancer cell lines by MTT-assay. Among the derivatives, (E)-4-benzylideneamino-1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines (1f: IC[Formula: see text] 23.7, and 6.4 [Formula: see text]M, respectively). The IC[Formula: see text] value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 [Formula: see text]M, which appeared to be 3-11-fold higher than IC[Formula: see text] values of 1f against human cancer cells.

First 3,5-diacetyl-1,2,4-triazol derived mono(thiosemicarbazone) and its palladium and platinum complexes: Synthesis, structure and biological properties

Preparation and characterization of 3,5-diacetyl-1,2,4-triazol mono(4-phenylthiosemicarbazone) ligand, H3L, and its derived palladium(II) and platinum(II) complexes, [Pd(HL)(PPh3)] and [Pt(HL)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The cytotoxicity of the new compounds synthesized was investigated in vitro against T-47D, A2780 and A2780cisR human cancer cell lines, being H3L the species with the highest activity. In addition, the DNA binding ability of H3L with calf thymus DNA was explored by UV–Vis absorption spectroscopy.

Synthesis and characterization of a new bioactive mono(thiosemicarbazone) ligand based on 3,5-diacetyl-1,2,4-triazol diketone and its palladium and platinum complexes

Preparation and characterization of a new 4N-p-chlorophenyl substituted thiosemicarbazone ligand, H3L2, and its derived palladium(II) and platinum(II) complexes, [Pt(HL2)(PPh3)] and [Pd(HL2)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The biological activity of the new compounds synthesized was initially explored by determining their antiproliferative activity in vitro against T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H3L2 since is capable not only to circumvent cisplatin resistance in A2780cisR cells but also to exhibit high antiproliferative activity in breast cancer T-47D cells.

Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes

The oxidation of human oxyhemoglobin (HbO2) to methemoglobin (metHb) is an undesirable side effect identified in some promising thiosemicarbazone anti-cancer drugs. This is attributable to oxidation reactions driven by FeIII complexes of these drugs formed in vivo. In this work the FeIII complexes of selected 2-benzoylpyridine thiosemicarbazones (HBpT), 2-acetylpyridine thiosemicarbazones (HApT), and the clinically trialled thiosemicarbazone, Triapine® (3-amino-2-pyridinecarboxaldehyde thiosemicarbazone, H3-AP), have been studied. This was achieved by time-resolved UV–Visible absorption spectroscopy and the sequential oxidation of the α- and β-chains of HbO2 at distinctly different rates has been identified. A key structural element, namely a terminal –NH2 group on the thiosemicarbazone moiety, was found to be an important common feature of the most active HbO2 oxidising complexes that were investigated. Therefore, these studies indicate that an unsubstituted –NH2 moiety at the terminus of the thiosemicarbazone group should be avoided in the design of future compounds from this class.

Design, synthesis and mode of action of novel 2-(4-aminophenyl)benzothiazole derivatives bearing semicarbazone and thiosemicarbazone moiety as potent antimicrobial agents

A novel series of substituted benzothiazoles, bearing semicarbazone and thiosemicarbazone moieties, was designed, synthesized and evaluated for their antimicrobial activity and possible mode of action. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, IR and Mass spectral data. The results revealed that compounds SC06, SC09, TS05 and TS07 have potent antibacterial activity against both Gram-positive and Gram-negative strains. Compound TS05 displayed most potent activity with MIC values of 3.91, 7.81 and 1.56 µg/ml against S. aureus, E. coli and P. aeruginosa, respectively. The results from cytoplasmic membrane permeabilization assay, FACS study as well as DNA-binding assays, evaluated against clinically relevant pathogens S. aureus and E. coli, suggest membrane perturbing as well as intracellular mode of action of this class of compounds. In addition, hemolytic activity of the compounds was measured which indicated their low cytotoxicity.

Crystal Structure and DFT Calculation Studies of Ni (II) Cinnamaldehyde Thiosemicarbazone Complex

Slow evaporation of a dilute DMSO solution of the title compound at room temperature, provided a brown crystal of Ni(CMTSC) 2 DMSO suitable for X-Rays study (space group: P-1, a(A)=8.1750 (3), b(A) =11.3400 (4), c(A) =15.1940 (5), α(°)=68.581 (3), β(°)=78.894(4), γ (°)=79.265(5)). Two Ni atoms were located on special positions providing two molecules of Ni(CMTSC) 2 which differ by torsion angles and intermolecular interactions. In both molecules, the thiosemicarbazone coordinates as an anionic ligand via the thiosemicarbazone moiety’s azomethine nitrogen and thiolatosulphur in a square-planar geometry. In the aim of investigate structural features, Density Functional Theory calculations of both ligand and complex were fully optimised with respect to the energy using B3LYP level. The predicted geometry parameters are compared with their corresponding X-ray crystallographic data.

Synthesis and spectral characterization of mono- and binuclear copper(II) complexes derived from 2-benzoylpyridine-N4-methyl-3-thiosemicarbazone: Crystal structure of a novel sulfur bridged copper(II) box-dimer

Mononuclear and binuclear copper(II) complexes of 2-benzoylpyridine-N4-methyl thiosemicarbazone (HL) were prepared and characterized by a variety of spectroscopic techniques. Structural evidence for the novel sulfur bridged copper(II) iodo binuclear complex is obtained by single crystal X-ray diffraction analysis. The complex [Cu2L2I2], a non-centrosymmetric box dimer, crystallizes in monoclinic C2/c space group and it was found to have distorted square pyramidal geometry (Addison parameter, τ=0.238) with the square basal plane occupied by the thiosemicarbazone moiety and iodine atom whereas the sulfur atom from the other coordinated thiosemicarbazone moiety occupies the apical position. This is the first crystallographically studied system having non-centrosymmetrical entities bridged via thiolate S atoms with Cu(II)I bond. The tridentate thiosemicarbazone coordinates in mono deprotonated thionic tautomeric form in all complexes except in sulfato complex, [Cu(HL)(SO4)]·H2O (1) where it binds to the metal centre in neutral form. The magnetic moment values and the EPR spectral studies reflect the binuclearity of some of the complexes. The spin Hamiltonian and bonding parameters are calculated based on EPR studies. In all the complexes g||>g⊥>2.0023 and the g values in frozen DMF are consistent with the dx2-y2 ground state. The thermal stabilities of some of the complexes were also determined.

Novel pyrazole–pyrazoline hybrids endowed with thioamide as antimalarial agents: their synthesis and 3D-QSAR studies

One of the most viable options to tackle the growing resistance to the antimalarial drugs is hybrid molecules. It involves combination of different scaffolds in one frame that may lead to compounds with diverse biological profiles. In this context, new hybrids of three different scaffolds viz pyrazole, pyrazoline and thiosemicarbazone moiety were incorporated into one single compound and evaluated for their in vitro schizontocidal activity against the CQ-sensitive 3D7 strain of Plasmodium falciparum. Compounds with significant in vitro antimalarial activity were further evaluated for cytotoxicity against VERO cell lines. The best active compound 48 exhibited an IC50 of 1.13 µM. The in vitro results were further validated by quantitative structure–activity relationship (QSAR).

Novel Bidentate [N,S] Palladacycle Metalloligands. 1H–15N HMBC as a Decisive NMR Technique for the Structural Characterization of Palladium–Rhodium and Palladium–Palladium Bimetallic Complexes

Treatment of tetranuclear palladacycles with 2-(diphenylphosphino)pyridine, Ph2Ppy, in acetone at room temperature for 10 h, gave the new bidentate [N,S] palladacycle metalloligands 1-7. Treatment of [Rh 2Cl2(CO)4] with AgClO4 in acetone at room temperature for 10 min, followed by addition of 1-7 and stirring at room temperature for 10 h, gave the novel heterobimetallic palladium-rhodium compounds 1a-7a as 1:1 electrolytes, where the new bidentate [N,S] palladacycle metalloligands are bonded to the second metal through the pyridine nitrogen atom, and the sulfur atom of the thiosemicarbazone moiety; they exhibit a six-membered bimetallic central ring of differing atoms. In a similar manner, reaction of [PdBr2(Ph2PR4PPh2)] (R4 = CH2, C=CH2, (CH2)2, cis-CH=CH) with AgClO4 in acetone at room temperature, followed by addition of 1-7, gave the homobimetallic palladium-palladium compounds, 2b, 3b, 5b-7b, and 5c-7c, as 1:2 electrolytes, also with [N,S] coordination of the corresponding metalloligand. 1H-15N HMBC experiments were a most valuable tool in helping to unequivocally ascertain rhodium-nitrogen and palladium-nitrogen coordination in the bimetallic species. The crystal and molecular structures of 3, 6, 2b, and 3b have been determined by X-ray crystallography; for compounds 3 and 3b, inter- and intramolecular interactions in the solid state result in crystal self-organization, leading to chains and/or layers in the molecular array. © 2014 American Chemical Society.

Synthesis, Crystal Structure, and Biological Activity of an Mn(II) Complex Derived from 2,6-diacetylpyridine bis(N 4-methylthiosemicarbazone)

Transition metal complex [Mn(H2L)(H2O)2](CH3COO)2 (1), where H2L = 2,6-diacetylpyridine bis(N 4-methylthiosemicarba- zone), has been synthesized and characterized by elemental analysis, IR, mass spectrometry, and single-crystal X-ray diffraction. Complex 1 is depicted as a monomeric, seven-coordinated complex formed with one Mn(II) ion, one pentadentate N3S2 thiosemicarbazone ligand, and two oxygen atoms from two water molecules. Biological studies, carried out in vitro against K562 leukemia cells, have shown that the thiosemicarbazone moiety and its manganese(II) complex show distinctive differences in the biological property.

Isothiocyanate analogs targeting CD44 receptor as an effective strategy against colon cancer.

Inflammatory pathway plays an important role in tumor cell progression of colorectal cancers. Although colon cancer is considered as one of the leading causes of death worldwide, very few drugs are available for its effective treatment. Many studies have examined the effects of specific COX-2 and 5-LOX inhibitors on human colorectal cancer, but the role of isothiocyanates (ITSCs) as COX-LOX dual inhibitors engaged in hyaluronan-CD44 interaction has not been studied. In the present work, we report series of ITSC analogs incorporating bioisosteric thiosemicarbazone moiety. These inhibitors are effective against panel of human colon cancer cell lines including COX-2 positive HCA-7, HT-29 cells lines, and hyaluronan synthase-2 (Has2) enzyme over-expressing transformed intestinal epithelial Apc10.1Has2 cells. Specifically, our findings indicate that HA-CD44v6-mediated COX-2/5-LOX signaling mediate survivin production, which in turn, supports anti-apoptosis and chemo-resistance leading to colon cancer cell survival. The over-expression of CD44v6shRNA as well as ITSC treatment significantly decreases the survival of colon cancer cells. The present results thus offer an opportunity to evolve potent inhibitors of HA synthesis and CD44v6 pathway and thus underscoring the importance of the ITSC analogs as chemopreventive agents for targeting HA/CD44v6 pathway.

Synthesis, Characterization, Crystal Structure, and Cytotoxicity of a Diorganotin(IV) Complex with 2-Acetylpyridine N 4-Phenylthiosemicarbazone

A new diorganotin(IV) complex formulated as [(Me)2Sn(L) (CH3COO)] (1), where HL = 2-acetylpyridine N(4)-phenylthiose micarbazone, has been synthesized and characterized by elemental analysis, IR spectra, and single-crystal X-ray diffraction studies. Schiff base in its deprotonated form coordinates to tin(IV) via pyridine nitrogen atom and the nitrogen atom and sulfur atoms of the thiosemicarbazone moiety. The tin(IV) ion is seven-coordinated and adopts a distorted pentagonal bipyramidal geometry. Biological studies, carried out in vitro against the K562 leukemia cells, have shown that the coupling of HL to Me2Sn(IV) leads to an enhancement of the cytotoxicity of the free ligand.

Nickel(II) complexes of polyhydroxybenzaldehyde N4-thiosemicarbazones: synthesis, structural characterization and antimicrobial activities

Nickel(II) complexes with 2,3-dihydroxybenzaldehyde N4-substituted thiosemicarbazone ligands (H3L1–H3L4) have been synthesized and characterized with the aim of evaluating the effect of N4 substitution in the thiosemicarbazone moiety on their coordination behavior and biological activities. Two series of nickel(II) complexes with the general formulae [Ni(H3L)(H2L)]ClO4 and [Ni2(HL)2] were characterized by analytical and spectral techniques. The molecular structure of one of the complexes, namely, [Ni(H3L4)(H2L4)]ClO4 was established by single crystal X-ray diffraction studies. The crystal structure of this complex revealed that two H3L4 ligands are coordinated to nickel(II) in different modes; one as a neutral tridentate ONS ligand and the other is as a monoanionic tridentate (ONS−) ligand. The antimicrobial activities of the compounds were tested against 25 bacterial strains via the disc diffusion method, and their minimum inhibitory concentration (MIC) and minimum microbicidal concentration were evaluated using microdilution methods. With a few exceptions, most of the compounds exhibited low-to-moderate inhibitory activities against the tested bacterial strains. However, the complexes [Ni2(HL3)2] (7) and [Ni2(HL4)2] (8) indicated higher inhibitory activity against Salmonella enterica ATCC 9068 (MIC values 15.7 and 50 μg/ml). The toxicities of the compounds were tested on brine shrimp (Artemia salina), where no meaningful toxicity level was noted for both the free ligands and the complexes. The cytotoxicities of the compounds on cell viability were determined on MCF7, PC3, A375, and H413 cancer cells in terms of IC50; complexes [Ni(H3L3)(H2L3)]ClO4 (3), [Ni2(HL3)2] (7) and [Ni2(HL4)2] (8) exhibited significant cytotoxicity on the tested cell lines.

Recycling of styrofoam waste: synthesis, characterization and application of novel phenyl thiosemicarbazone surface

Abstract An attempt has been made to recycle Styrofoam waste to a novel functional polymer, Phenyl thiosemicarbazone surface (PTS). Polystyrene (PS) obtained from Styrofoam waste was acetylated and then condensed to PTS by reacting it with 4-Phenyl-3-thiosemicarbazide ligand and characterized by FT-IR spectroscopy and elemental analysis. Synthesized PTS was applied successfully for the treatment of lead contaminated water by batch extraction method. Sorption variables were optimized (pH 8, adsorbent dose 53mg, initial Pb(II) ion concentration 10mgl-1 and agitation time 90min) by factorial design approach. Lead uptake by PTS was found much sensitive to the pH of Pb(II) ion solution. The maximum removal (99.61%) of Pb(II) ions was achieved at optimum conditions. The Langmuir and D-R isotherm study suggested the monolayer, favorable (RL=0.0001-0.01) and chemisorption (E=20.41±0.12kJmol-1) nature of the adsorption process. The sorption capacity of PTS was found to be 45.25±0.69mgg-1. The FT-IR spectroscopy study showed the involvement of nitrogen and sulphur of thiosemicarbazone moiety of PTS for the uptake of Pb(II) ions by five membered chelate formation.

4-(Diphenylamino)benzaldehyde 4-phenylthiosemicarbazone

The title mol­ecule, C26H22N4S, is composed of three main parts, viz. a triphenyl­amine group is connected to a phenyl ring by a thio­semicarbazone moiety. The C= N double bond has an E conformation. The crystal packing is dominated by strong hydrogen bonds through the thio­semicarbazone moiety, with pairs of N—H⋯S hydrogen bonds linking the mol­ecules to form inversion dimers with an R 2 2(8) ring motif. An intra­molecular N—H⋯N hydrogen bond is also present, generating an S(5) ring motif. Although the structure contains four phenyl rings, π–π stacking inter­actions are not formed between them, probably due to the conformation adopted by the triphenyl­amine group. However, a weak π–π stacking inter­action is observed between the phenyl ring and the delocalized thio­semicarbazone moiety.

Synthesis and evaluation of fluorimetric and colorimetric chemosensors for anions based on (oligo)thienyl-thiosemicarbazones

A family of heterocyclic thiosemicarbazone dyes (3a–d) containing thienyl groups has been synthesized, characterized, and their chromo-fluorogenic response in acetonitrile in the presence of selected anions was studied. Acetonitrile solutions of 3a–d show absorption bands in the 338–425 nm range, which are modulated by the groups attached to the thiosemicarbazone moiety. The fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulfate, nitrate, acetate, and cyanide anions were used in the recognition studies. Only sensing features were observed for fluoride, cyanide, acetate, and dihydrogen phosphate anions. Two different chromogenic responses were found, (i) a small shift of the absorption band due to coordination of the anions with the thiourea protons and (ii) the appearance of a new red-shifted band due to deprotonation of the receptor. For the latter process changes in the color solutions from pale-yellow to orange-red were observed. Fluorescence studies showed a different emission behavior according to the number of thienyl rings in the π-conjugated bridges. Stability constants for the two processes (complex formation+deprotonation) for receptors 3a–d in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec program. The interaction of 3d with fluoride was studied through 1H NMR titrations. Semiempirical calculations to evaluate the hydrogen-donating ability of the receptors were also performed.

Synthesis and Biological Evaluation of Some New N4-Aryl Substituted 5-Chloroisatin-3-thiosemicarbazones

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.